Scientia Pharmaceutica doi: 10.3390/scipharm94040095

Authors: Araceli Morales-Hernández Ana Carolina Tirado-Garibay Alejandra Ochoa-Zarzosa Joel Edmundo López-Meza

Metastasis is responsible for the majority of cancer-related deaths. During metastasis, cancer cells undergo a series of biological events that allow them to invade surrounding tissues, disseminate through the bloodstream or lymphatic system, and colonize secondary sites. Cancer cells’ phenotypic plasticity facilitates this process by enabling them to adapt to diverse microenvironments. Unlike localized tumors, metastasis is more challenging to treat because it represents a systemic disease that can no longer be managed solely through surgery or radiotherapy. Additionally, specific mechanisms underlying metastasis may contribute to resistance to conventional chemotherapy. Therefore, identifying new therapeutic strategies to regulate the key processes underlying metastasis is essential. In recent years, antimicrobial peptides (AMPs) have garnered increasing interest because of their anticancer properties. AMPs are small molecules that are part of the innate immune system of virtually all living organisms and are characterized by their ability to selectively interact with the cell membranes of pathogens and cancer cells. Diverse AMPs have been shown to induce cancer cell death, inhibit proliferation, and interfere with processes associated with metastasis. This review discusses the potential of AMPs as metastasis modulators, highlighting their proposed mechanisms of action, their advantages over conventional therapeutic approaches, and the conceptual framework governing their dual pro- and anti-metastatic activities.

Scientia Pharmaceutica doi: 10.3390/scipharm94040094

Authors: Alejandra Yoselin González-Muñiz Martha Cecilia Rosales-Hernández Ruth Esther Villanueva-Estrada Luis Arturo Soto Silvia Laura Guzmán-Gutiérrez Francisco Javier Pérez-Flores Ricardo Reyes-Chilpa Mónica Adriana Torres-Ramos

Hydrothermal vent communities are a source of bioactive compounds; some of these could be a potential anticancer therapy. Riftia pachyptila is a marine invertebrate endemic to hydrothermal vents. The dichloromethane–methanol (1:1) extracts were obtained from the wall (Pa), the trophosome (Tr), and the tube (Tu) of R. pachyptila. The cytotoxic effect of extracts was evaluated on human glioblastoma cell lines U373 and U87 and fibroblast BJ1 cell line by MTT and trypan blue assays. To detect DNA apoptotic fragmentation and tumoral p53 expression by Pa, the TUNEL and immunofluorescence assays were performed, respectively. The extracts were analyzed by gas chromatography–mass spectrometry. The Pa extract produced the most cytotoxicity on U87 and U373 cells, but not on BJ1 cells; furthermore, Pa extract produced apoptosis and cytosolic p53 stabilization. The chemical profile of extracts showed thirty-four natural compounds. This study identifies R. pachyptila extracts as potential source of drugs for glioblastoma.

Scientia Pharmaceutica doi: 10.3390/scipharm94040093

Authors: Yuriy Karpenko Volodymyr Parchenko Borys Kyrychko Liudmyla Kucherenko Olena Ishchenko Iryna Pukhalska Tetiana Chetvertak Daria Safronova Mykola Shumeiko

Chronic and difficult-to-heal wounds require topical agents that combine reparative activity with favorable local disposition and an acceptable preliminary safety profile. This study evaluated three orotic acid–1,2,4-triazole hybrids (1–3) using an integrated computational and experimental workflow. Accelerated weight histogram simulations were performed in an atomistic human stratum corneum lipid model; acute toxicity was assessed by in silico rat LD50 prediction, 96 h Danio rerio LC50 testing, and OECD 425 oral testing in rats. Compounds selected on the basis of toxicity were incorporated into electrospun polyvinylpyrrolidone K-30 dressings and evaluated in a rat excisional wound model. Compound 1 showed pronounced lipid partitioning and potential intralamellar retention, whereas compounds 2 and 3 encountered broad membrane-interior free-energy barriers. Compound 2 had the least favorable acute-toxicity profile and was excluded. By day 8, wound area decreased by 89.0% with compound 1 and 78.6% with compound 3, versus 70.5% with the drug-free vehicle dressing (p < 0.001 for both comparisons). Neither treatment caused clinically evident deterioration or a consistent biochemical pattern of marked hepatic or renal dysfunction, although hematological and compound-specific biochemical changes were observed. The compound 1-loaded dressing therefore warrants further mechanistic, histological, and longer-term safety evaluation as the lead formulation.

Scientia Pharmaceutica doi: 10.3390/scipharm94040091

Authors: Bhagavathi Sundaram Sivamaruthi Pranom Fukngoen Chaiyavat Chaiyasut Periyanaina Kesika Nallasamy Prakashkumar Natarajan Suganthy Suchanat Khongtan

Beta-amyloid peptide (Aβ), the key pathogenic factor of Alzheimer’s disease (AD), induces oxidative stress-mediated neuronal damage, eventually leading to death. Madecassic acid (MAD), a natural triterpenoid isolated from Centella asiatica, has been reported for many biological activities, including neuroprotective effects. The low solubility and poor bioavailability of MAD are major limitations; hence, the present study focused on formulating MAD in a nanostructured lipid carrier (NLC-MAD) and evaluating its protective effect against oxidative stress induced by Aβ (25–35) in Neuro-2A cells. NLC-MAD, made of 7.5% total lipid, 50% liquid oil, and 6% surfactant with desirable qualities, was selected for further studies. NLC-MAD exhibited potent free radical scavenging activity (IC50 value 80.20 ± 0.05 μg/mL), reducing power, total antioxidant power, and metal chelating activity (IC50 value 120.12 ± 0.02 µg/mL). NLC-MAD showed a dose-dependent inhibition of acetyl and butyrylcholinesterase with IC50 values of 12.5 ± 0.001 and 30 ± 0.02 µg/mL, respectively. NLC-MAD attenuated Aβ peptide aggregation and disaggregated the preformed mature fibrils. NLC-MAD pretreated Neuro-2A cells attenuated Aβ-induced toxicity dose-dependently and attenuated oxidative stress-mediated toxicity. Safety evaluation studies revealed that NLC-MAD is neither cytotoxic nor hemolytic under in vitro conditions and exhibited no adverse effects under in vivo conditions, indicating a non-toxic nature. The results warrant further studies on the stability of NLC-MAD and preclinical studies before consideration to clinical trials.

Scientia Pharmaceutica doi: 10.3390/scipharm94040092

Authors: Carmen-Maria Jîtcă George Jîtcă Lenard Farczadi Silvia Imre

Bisoprolol and Lisinopril are among the most frequently used substances in pediatric cardiovascular affections. The medication supply to this age population is limited given the lack of appropriate pharmaceutical forms; therefore, pharmaceutical compounding comes to fill in the gap between pediatric therapy needs and availability of adult-approved formulations. The aim of our study was to obtain and quantify two suspensions of Bisoprolol and Lisinopril in small pediatric dosage. The suspensions were obtained using a commercial suspending vehicle and the active substances. We developed the quality control methods according to the USP. Briefly, both methods were developed and validated using a UHPLC Flexar 10 system (Perkin Elmer) equipped with a Phenomenex Luna C8 column (150 × 4.6 mm, 3 μm) under isocratic conditions at a flow rate of 1 mL/min. For bisoprolol, the mobile phase consisted of water (65:35, v/v) with the specified additives, with detection at 273 nm, while lisinopril was analyzed using 10 mM ammonium formate buffer (pH 5) (96:4, v/v), with detection at 210 nm. The calibration ranges were 30–90 μg/mL for bisoprolol and 20–100 μg/mL for lisinopril. We obtained satisfactory results for method validation, and the method was applied for the assay of two types of suspensions. The obtained results ranged between 80 and 86% of the labeled amounts for Bisoprolol, and 106–108% for Lisinopril. The obtained suspensions reflected some issues related to the sample extraction and potential variability in suspension sampling and dosing consistency, which support the need for continuous optimization and quality control of compounded pediatric formulation.

Scientia Pharmaceutica doi: 10.3390/scipharm94040090

Authors: Duaa Abuarqoub Alqassem H. Abuarqoub Mais Emad Majd F. Ellauzi Pascal A. Hattar

Natural phenolic compounds are plant-derived compounds known for their potent antioxidant and anti-inflammatory properties. In addition, natural phenolic compounds are being investigated for their potential applications in pain management, and tissue engineering and regenerative medicine. This review aims to emphasize the anti-inflammatory and anti-oxidant effects of natural phenolic compounds and to highlight their important roles in pain management and tissue engineering and regenerative medicine. In pain management, natural phenolic compounds demonstrated promising results in suppressing orofacial, pelvic, neuropathic, and musculoskeletal pain compared to conventional pain management drugs or by synergistically acting with those drugs. While in tissue engineering and regenerative medicine, natural phenolic compounds were found to enhance the differentiation potential of stem cells into different lineages by increasing the expression of differentiation markers and were also found to enhance proliferation and migration of different types of dental stem cells. In conclusion, natural phenolic compounds, due to their unique properties, are promising in protocols of pain management as well as in tissue engineering and regenerative medicine.

Scientia Pharmaceutica doi: 10.3390/scipharm94040089

Authors: Mohammad Khurshed Alam Khan Pratikshya Paudel Prabir Kumar Gharai

Flavonoids are plant-derived polyphenols found in fruits, vegetables, tea and other dietary sources. Global dementia prevalence is projected to rise sharply, and current disease-modifying therapies remain limited in efficacy. This gap has contributed to growing interest in dietary flavonoids as multi-target neuroprotective agents. This review draws together mechanistic, preclinical, and early clinical evidence for six flavonoid subclasses (flavanones, flavonols, flavones, flavanols, anthocyanins, isoflavones) across five neuroprotective mechanisms: antioxidant defense, suppression of neuroinflammation, inhibition of pathogenic protein aggregation, promotion of neurogenesis and synaptic density, and preservation of blood–brain barrier integrity. We also summarize proposed structure–activity relationships linking substitution patterns (catechol groups, hydroxylation, glycosylation) to these mechanisms. Most of this evidence comes from in vitro and rodent models. Longitudinal cohorts do link dietary intake to slower cognitive decline, but clinical trials remain few, early-phase, and inconsistent; some report negligible change on clinical metrics such as the UPDRS scale. Certain flavonoid metabolites are detected in rodent brain tissue after oral dosing, though whether humans achieve pharmacologically meaningful brain exposure at dietary or supplemental doses is still unresolved. Translation faces substantial barriers: limited oral bioavailability, extensive first-pass metabolism, inconsistent blood–brain barrier penetration, and wide inter-individual variability in metabolism, gut microbiome composition, and trial design. We close by outlining strategies, including nanoparticle delivery, prodrug design, and precision nutrition approaches, that could move flavonoids closer to clinical relevance.

Scientia Pharmaceutica doi: 10.3390/scipharm94040088

Authors: Petr Mlejnek Petr Dolezel

Lysosomal exocytosis induced by the sequestration of hydrophobic weak-base drugs has been proposed as a mechanism of drug resistance (DR), although direct evidence for its quantitative relevance is lacking. Here, we compared the kinetics of lysosomal exocytosis with those of ABCB1-mediated active drug efflux and passive drug efflux by diffusion in K562 cells. Drug panels were selected according to the process investigated, with passive efflux assessed using compounds representing both the lysosomal exocytosis and ABCB1 substrate groups. Lysosomal exocytosis was quantified using FITC-dextran-labelled lysosomes and flow cytometry. K562 cells with high or moderate ABCB1 expression were used to determine active efflux, whereas parental K562 cells lacking detectable ABCB1 expression were used to determine passive efflux. Drug-induced lysosomal exocytosis was slow, with the intracellular FITC-dextran content decreasing to approximately 50% of its initial value after 5–8 h at 30 μM and 8–12 h at 10 μM. In contrast, ABCB1-mediated and passive efflux exhibited half-times of approximately 12–20 and 23–36 min, respectively. Moreover, measurable lysosomal exocytosis occurred only at high micromolar drug concentrations associated with off-target cytotoxicity. Thus, lysosomal exocytosis is unlikely to represent a quantitatively relevant mechanism of drug resistance in K562 cells.

Scientia Pharmaceutica doi: 10.3390/scipharm94040087

Authors: Magdalena Podolak Rostyslav Dudchak Agnieszka Gornowicz Olga Klaudia Szewczyk-Roszczenko Yegor Vassetzky Małgorzata Borzym-Kluczyk Krzysztof Bielawski Roman Lesyk Anna Bielawska

4-Thiazolidinone derivatives, a group of compounds with a broad spectrum of activity and anticancer properties, are used in medicine as anti-inflammatory, antiviral, antibacterial, antidiabetic, and blood pressure-lowering drugs; some of them are now in phase II and III clinical trials as anticancer drugs. Here, we evaluated the anticancer potential of 4-thiazolidinones (2b, 12b, 14b) targeting tubulin and metastasis-related pathways in breast cancer models. Molecular docking revealed that compound 14b exhibited the strongest binding affinity to the paclitaxel-binding site of β-tubulin, outperforming 2b and 12b, though slightly weaker than Taxol. Biological assays confirmed significant tubulin inhibition, with 14b reducing β-tubulin levels up to eight-fold in MCF-7 cells and two-fold in MDA-MB-231 cells. All compounds promoted tubulin polymerization, showing paclitaxel-like activity, with comparable the maximum velocity (Vmax) values. Cell cycle analysis demonstrated G2/M arrest in MCF-7 cells and S-phase accumulation in MDA-MB-231 cells. Overall, compound 14b demonstrated the most promising multitarget anticancer activity in vitro.

Scientia Pharmaceutica doi: 10.3390/scipharm94040086

Authors: Mohammad Hossain Stephen M. Markley Jaqueline Pena-Zacarias Jacquelynn J. Wiles Jolie N. Dionne Renato J. Aguilera Jonathan R. Dimmock

Three series of benzylidene cinnamoylhydrazides (21 compounds) were synthesized and evaluated for cytotoxic activity against malignant and non-malignant cell lines. Among the compounds tested, 2d and 3c were the most active against Jurkat and CEM leukemia cells, with CC50 values in the low micromolar range. Both compounds were more potent against these leukemia cell lines than the reference compounds 5-fluorouracil, curcumin, and melphalan. However, 2d and 3c showed only modest selectivity over non-malignant Hs27 fibroblasts, with selectivity index values of 2.50 and 2.09, respectively, in CEM cells. Further studies in CEM cells showed that treatment with 2d and 3c was associated with apoptosis, caspase activation, increased ROS accumulation, mitochondrial membrane depolarization, and changes in cell-cycle distribution, with the most notable change being an increase in the sub-G0-G1 population. The compounds also showed growth-inhibitory and cytotoxic activity against several cell lines in the NCI-60 panel. Semi-empirical PM3 calculations suggested possible relationships between cytotoxic activity, electronic polarization of the α,β-unsaturated carbonyl system, and molecular dimensions. However, these relationships were not consistent across the series and should be considered preliminary. Overall, 2d and 3c represent useful hit structures for further investigation, although additional structural optimization and biological studies will be needed to improve their selectivity and better define their mechanisms of action.

Scientia Pharmaceutica doi: 10.3390/scipharm94040085

Authors: Mayara C. dos Santos Átila M. Mofati Nathalia F. Nadur Larissa de A. P. Ferreira Lucas Caruso Gleyton L. S. Sousa Renata B. Lacerda Arthur E. Kümmerle

Alzheimer’s disease (DA) remains a major therapeutic challenge, and selective butyrylcholinesterase (BChE) inhibition has emerged as a promising strategy for symptomatic treatment, particularly in advanced stages. Herein, a series of novel quinoline–acylguanidine hybrids was designed through a bioisosteric replacement of acridine–thiosemicarbazones and synthesized via a convergent route combining the Pfitzinger reaction with acylguanidine formation. All derivatives were evaluated against BChE and AChE (acetylcholinesterase), and the 2-phenylquinoline derivative 2c (IC50 = 7.14 µM) was identified as the most potent BChE inhibitor, comparable to donepezil (IC50 = 2.39 µM), with selectivity over AChE. Structure–activity relationships revealed that the 2-phenyl substituent is essential for activity, whereas bulky groups (4-bromophenyl) or replacement with methyl abolished inhibition. Molecular docking showed that active compounds bind within the BChE catalytic anionic site with Trp110, Met465, and Trp458, while inactive analogs undergo a 180° flip of the quinoline scaffold, disrupting key interactions. In silico ADME evaluation indicated a favorable CNS drug-like profile (TPSA < 90 Å2, LogBB > −1, no Lipinski violations, and no predicted P-glycoprotein substrate liability). These findings establish the quinoline–acylguanidine scaffold as a promising new chemotype for the development of selective BChE inhibitors with potential applications in Alzheimer’s disease.

Scientia Pharmaceutica doi: 10.3390/scipharm94040084

Authors: Taye Bello Vladislav Turenko Andrey Goryachev Irina Remezova Daniil Dolgov George Pasikhov Sergey Dementev Vladimir Gegechkori Yana Poskedova Timofey Smirnov Olga Petukhova Musa Khaitov Valery Smirnov

Ragweed (Ambrosia artemisiifolia) pollen allergy is a major and growing public health problem worldwide, with clinical manifestations ranging from rhinitis and conjunctivitis to asthmatic episodes and anaphylaxis. The major ragweed allergen, Amb a 1, exhibits high IgE-binding potential and triggers type 1 hypersensitivity reactions. Although allergen-specific immunotherapy (AIT) effectively induces long-term immune tolerance, conventional extract-based formulations face critical limitations including batch-to-batch variability, heterogeneous allergen composition, IgE-mediated adverse reactions, inconsistent immunogenicity, and poor patient compliance. This critical review synthesizes and evaluates published evidence on current synthetic vaccine strategies for ragweed AIT, with emphasis on their design, immunological performance, and quality control considerations. This review critically evaluates current approaches to synthetic vaccine development for ragweed AIT, with a particular focus on peptide-based constructs, recombinant proteins, DNA vaccines, and adjuvant-enhanced formulations, alongside corresponding quality control strategies. The available evidence indicates that synthetic vaccines provide a more rational, molecularly characterized trajectory for producing optimized AIT products with improved safety profiles, enhanced clinical efficacy, reduced injection frequency, and improved batch standardization relative to extract-based immunotherapy. These advances highlight the potential of synthetic vaccine platforms to support personalized immunotherapy and more effective disease-modifying treatment of allergic disorders.

Scientia Pharmaceutica doi: 10.3390/scipharm94030083

Authors: Adelphe Dounia Jean Noël Nyemb Romeo Toko Feunaing Cyrille Tchuente Djoko Samiran Sadhukan Sophie Laurent Céline Henoumont Emmanuel Talla

Background: Plasmodium falciparum, the most virulent malaria parasite, continues to develop resistance to available drugs. Mitragyna inermis (Rubiaceae) is traditionally used in Africa for the treatment of malaria and has shown antiplasmodial activity against P. falciparum. Previous studies on this plant and related species (M. speciosa, M. ciliata) have focused on crude extracts and indole alkaloids, reporting moderate antiplasmodial activity, but the specific contribution of pure quinovic acid glycosides, the major triterpenes glycosides of M. inermis stem bark, to antiplasmodial activity and to inhibition of key parasite enzymes such as lactate dehydrogenase (PfLDH) and protein kinase G (PfPKG) has never been evaluated. Objective: The present study aimed to isolate and characterize compounds from the stem bark of M. inermis and to evaluate their antiplasmodial activity against Pf3D7 and PfDd2 strains and their binding potential to PfLDH and PfPKG through experimental and computational approaches. Methods: Phytochemical investigation was conducted using column chromatography, and structures were elucidated by ESI-MS and 1/2D NMR spectroscopy. Antiplasmodial activity was assessed against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfDd2) strains of P. falciparum. Molecular docking, ADMET prediction, and 100-ns molecular dynamics simulations targeting PfLDH and PfPKG were performed. Results: Five compounds were isolated and identified as quinovic acid 3-O-β-D-fucopyranoside (1), quinovic acid 3-O-β-D-glucopyranoside (2), quinovic acid 3β-O-β-D-fucopyranosyl-28-O-β-D-glucopyranosyl ester (3), olean-12-ene-3β,19β,24-triol (4), and lupeol-3-O-undecanoate (5). Compounds 4 and 5 are reported for the first time from the genus Mitragyna. Compound 3 exhibited the highest antiplasmodial activity against both PfDd2 (35.86 ± 0.83 μM) and Pf3D7 (29.89 ± 3.91 μM) strains, and showed the strongest binding affinity toward PfLDH (−8.2 kcal/mol). MD simulations confirmed the stability of the C3_PfLDH complex throughout the 100 ns simulation period. Conclusions: Compounds 1–4 displayed moderate in vitro antiplasmodial activity against Pf3D7 and PfDd2, with compound 3 being the most active among the isolated constituents. Docking and molecular-dynamics analyses suggested stable interactions of selected compounds with PfLDH and the PfPKG N-terminal cGMP-binding domain. However, these computational findings do not establish direct enzyme inhibition. The results support further investigation of M. inermis triterpenoids as phytochemical scaffolds, including cytotoxicity/selectivity testing, direct target-based assays and structural optimization.

Scientia Pharmaceutica doi: 10.3390/scipharm94030082

Authors: María José Jiménez Keyner De La Cruz Reinaldo G. Sotomayor

Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID) with antipyretic, analgesic, and anti-inflammatory activity; however, its low aqueous solubility limits its dissolution rate and, consequently, its oral bioavailability. This study aimed to develop and physicochemically characterize an ibuprofen-loaded self-nanoemulsifying drug delivery system (SNEDDS) using a Box–Behnken experimental design. Fifteen formulations were prepared and evaluated based on CQAs: cloud point, robustness to dilution, self-emulsification time, droplet size, zeta potential, and polydispersity index (PDI). The experimental responses were subjected to statistical analysis; robustness to dilution as the only response yielding a statistically valid and predictive model within the studied design space, which was used as the sole optimization criterion. The optimal formulation was evaluated and characterized according to previously established CQAs and subjected to thermodynamic stability testing and stress testing over one month. The optimized formulation exhibited rapid self-emulsification, with a self-emulsification time of 37.02 s, a cloud point of 64.87 °C, and high robustness to dilution across different pH conditions and dilution volumes. Moreover, it exhibited a mean droplet size below 157 nm, a zeta potential of −15.43 ± 0.58 mV, and a PDI of 0.251, suggesting adequate colloidal stability and uniformity of the dispersed system. These physicochemical attributes support the potential of the developed system as a platform for further biopharmaceutical evaluation of ibuprofen oral delivery.

Scientia Pharmaceutica doi: 10.3390/scipharm94030081

Authors: Joanne Palomino Saavedra Yina Pájaro González Donaldo de la Hoz Santander Edwin Enrique Tenorio Jiménez Orison Hernández Gámez Gina Paola Domínguez Moré

Vancomycin (VCN) is a glycopeptide antibiotic widely used to treat Gram-positive infections such as those caused by methicillin-resistant Staphylococcus aureus (MRSA). Its narrow therapeutic window, high interindividual pharmacokinetic variability, and dose-dependent nephrotoxicity support the need for therapeutic drug monitoring (TDM). In this study, a UHPLC-UV method for VCN quantification in human plasma was developed and validated according to ICH M10 guidelines, using a one-step protein precipitation requiring only 100 µL of plasma. Clinical applicability was preliminarily explored in three hospitalized patients, where the area under the concentration-time curve over 24 h to minimum inhibitory concentration ratio (AUC24/MIC) was estimated using PrecisePK, NextDose, and TDMx Bayesian software platforms before and after dose adjustment. The method showed linearity from 0.5 to 100 µg/mL (r2 > 0.99), with accuracy within ±7% and precision below 11%. Acceptance criteria for selectivity and matrix effect were met, and stability was confirmed under multiple conditions, including clinically relevant storage and transport. Pre-adjustment AUC24/MIC values were outside the target window of 400–600 in all patients, confirming the pertinence of implementing model-informed precision dosing as a routine TDM practice in Colombian health institutions.

Scientia Pharmaceutica doi: 10.3390/scipharm94030080

Authors: Silvana Alfei Maria Luisa Cristina Marina Sartini Gianluca Ottria Guendalina Zuccari Caterina Reggio Anna Maria Schito

Multidrug resistance (MDR) has become a major global health threat, leading to the emergence of difficult-to-treat bacterial “superbugs” among both Gram-positive and Gram-negative species. In hospital settings, biofilm (BF)-producing staphylococci further aggravate this problem by markedly increasing tolerance to conventional antibiotics, thereby promoting chronic and potentially life-threatening infections. In the present study, previously synthesized and characterized 1,12-bis-triphenyl phosphonium dodecane bromide nanovesicles (BPPB, 45 nm, water) were assayed by DLS in a medium (TSB), which was used for microbiologic tests, to assess the actual particle size (≈65 nm) existing in this biological setting, with PDI (0.37) and zeta potential (+6.1 mV). Although never investigated for its effects on the formation of staphylococcal BF, BPPB was, for the first time, evaluated as a potential novel agent to combat its development. A total of 12 highly BF-producing isolates from our collection, comprising six Staphylococcus aureus and six S. epidermidis strains, were selected because they are strong BF producers. Their full antibiogram was determined, and they were tested against BPPB to determine minimum inhibitory concentrations (MICs). Subsequently, BF inhibition activity was evaluated at ½ MIC, MIC, and 2× MIC concentrations. Vancomycin (V), used as a reference antibiotic, was tested under the same experimental conditions. BPPB exhibited MIC values ranging from 0.125 to 0.250 µg/mL, which were 1–8-fold lower than those of V. V did not inhibit BF formation by S. epidermidis at all and inhibited BF formation by Bam and Aam S. aureus isolates (96–97% inhibition) only at max concentrations (2 × MIC). Conversely, BPPB demonstrated potent and consistent inhibition activity against all strains, irrespective of species or resistance profile, as determined by VITEK. BF inhibition values of 83–99%, 95–>99%, and 98–>99% were observed at ½ MIC, MIC, and 2 × MIC, respectively. To confirm that BF inhibition did not arise from killing bacteria, determinations of bacterial colony count after BPPB treatment at 4 × MIC for 24 h were performed, establishing full vitality and a regrowth of 45% with respect to the inoculum. Once reseeded as in the control, treated bacteria grew exactly as the control. Overall, the findings confirmed the nanosized dimension of BPPB particles, which remained <100 nm, including in the complex biological medium; this highlighted the strong BF-forming capability and MDR phenotype of the selected staphylococcal isolates, as well as the remarkable antibacterial and BF inhibition efficacy of BPPB nanovesicles, significantly outperforming vancomycin. Importantly, the low cytotoxicity previously observed against eukaryotic Cos-7 and HepG2 cells, resulting in high selectivity index (SI) values (23.0–90.5), supports BPPB as a promising candidate for the development of new NM-based therapeutic strategies against MDR staphylococcal BF-associated infections.

Scientia Pharmaceutica doi: 10.3390/scipharm94030079

Authors: Edgar Sandoval-Petris Rosalio Ramos-Payan Hisila del Carmen Santacruz-Ortega Maribel Plascencia-Jatomea María Guadalupe Burboa-Zazueta Idalia Osuna-Ruíz Elsa Maribel Aguilar-Medina Carmen María López-Saiz

Compounds isolated from the macroalga Caulerpa sertularioides have been reported to exhibit cytotoxic activity. The objective of this study was to assess the antioxidant effects of compounds isolated from C. sertularioides as well as their antiproliferative effect against cancerous cell lines and to elucidate their chemical structure. The antiproliferative activity of C. sertularioides extracts was evaluated using the MTT standard assay in cancerous and non-cancerous cell lines. Morphological changes were observed via fluorescence microscopy, and the chemical structure of bioactive compounds was determined by nuclear magnetic resonance. Antioxidant activity was assessed using ABTS and DPPH methods. Among all extracts, the acetone extract exhibited the highest antioxidant activity (IC50 of 27.3 ± 6.1 μg/mL) in the ABTS assay, which classifies it as a very potent antioxidant. Among the tested extracts, the hexane extract showed the strongest antiproliferative activity in breast (MDA-MB-231) and cervical cancer (HeLa) cell lines. The most active fraction (F15), obtained by open-column chromatography of hexane extract, exhibited the highest bioactivity against the MDA-MB-231 cell line (IC50 of 55 ± 3.1 µg/mL); these cells exhibited morphological changes consistent with apoptosis. NMR analysis revealed signals tentatively assigned to 1-monolinolein, glycerol, bis(2-ethylhexyl) phthalate and bis(2-ethylhexyl) terephthalate. These findings support the potential of C. sertularioides as a source of bioactive compounds with antioxidant and antiproliferative properties.

Scientia Pharmaceutica doi: 10.3390/scipharm94030078

Authors: Adrian Stan Sorina Nicoleta Munteanu Alina Plesea-Condratovici Liliana Mititelu-Tartau Beatrice Rozalina Buca Aurelia Romila Liliana Lacramioara Pavel Mihaela Moisei

Monoclonal antibody-based therapies are widely used in chronic immune-mediated diseases, but their periodontal effects, dentoalveolar safety signals, and exposure characteristics remain incompletely characterized. This scoping review mapped periodontal clinical outcomes, biomarkers, microbiological and imaging findings, dentoalveolar safety, administration, treatment exposure, and pharmaceutical-context reporting. PubMed, Scopus, and Web of Science were searched in July 2026 without publication-year or language restrictions. Twenty-one reports representing 20 studies or cohort families were included. Evidence mainly concerned rheumatoid arthritis and therapies targeting tumor necrosis factor, interleukin-6 receptor, and cluster of differentiation 20. Evidence for interleukin-17A inhibition was insufficient and derived from one confounded five-patient case series. Tocilizumab showed the most consistent reductions in gingival inflammation and bleeding on probing, while structural changes were smaller and inconsistent. Tumor necrosis factor-directed findings were heterogeneous. Small rituximab studies showed favorable clinical or biomarker signals, whereas pharmacovigilance identified infectious and destructive dentoalveolar signals. Exposure reporting was incomplete, and no included periodontal study evaluated formulation stability, storage, cold-chain integrity, or handling deviations. This review integrates treatment-effect evidence, safety signals, and exposure variables across antibody targets and identifies a pharmaceutical–periodontal reporting gap requiring prospective investigation.

Scientia Pharmaceutica doi: 10.3390/scipharm94030077

Authors: Eirini Roungeri Evangelia K. Konstantinou Kallirroi Dimiza Maria Dimitriou Anastasios Darras Athanasios A. Panagiotopoulos

Cancer is still one of the major causes of death globally. While there are many cancer therapies, they often come with significant adverse effects and limitations. A lot of studies have shown that using natural products can improve the efficacy of conventional therapies and decrease their toxicity. Natural products and their derivatives encompassing unmodified molecules, semi-synthetic analogs, and synthetic structures featuring natural pharmacophores, represent a major foundation for approved anticancer agents. Phenolic compounds are a large family of naturally occurring compounds found in plants and have attracted a lot of attention for their potential anticancer properties. Preclinical studies have shown that phenolic compounds have anticancer activity through different mechanisms, mainly by modulating inflammation, which plays a critical role in cancer development. Inflammatory processes in cancer involve complex molecular mechanisms regulated by both oncogenic and tumor-suppressing transcription factors. This review focuses on how phenolic compounds regulate transcription factors, such as nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and signal transducer and activator of transcription 3 (STAT3), which are critical in cancer-related gene expression, ultimately leading to the inhibition of cancer cell proliferation, invasion, and metastasis. Furthermore, phenolic compounds have been shown to synergize with conventional anticancer drugs, enhancing their efficacy and reducing side effects. This review investigates the role of phenolic compounds in regulating transcription factors in cancer animal models, highlighting both the therapeutic potential and limitations of these compounds in cancer prevention and treatment.

Scientia Pharmaceutica doi: 10.3390/scipharm94030076

Authors: Paulina Sánchez-Toledo Rosa M. Salgado Silvestre Ortega-Peña Edgar Krötzsch

Introduction: Heavily exuding wounds can macerate perilesional skin and favour infection. Information on the properties and use time of dressings should be clear and available to healthcare providers. Methods: Our aim was to evaluate the updated series of the AQUACEL® dressing family, because their evolution from a single layer of carboxymethylcellulose (NaCMC) to a multicomponent antiseptic or its combination with polyurethane covered with a silicon layer has developed the technology beyond simple exudate absorption. Using gravimetric analysis, we evaluated the porosity, water uptake, and water vapour transmission rate (WVTR) of AQUACEL® Ag+Extra, AQUACEL® Foam, and Foam Pro. By modifying the method of measuring WVTR, we assessed this outcome during the progressive saturation of the dressings. We also performed a disc diffusion assay on agar to determine the antimicrobial effects of the dressings. Results: Independently of porosity, a second layer of cellulose in AQUACEL® Ag+Extra doubles water uptake and quadruples WVTR compared to foam forms. When the different dressings were evaluated for WVTR under progressive saturation, we did not observe any statistically significant changes, indicating that retained liquids do not alter dressing properties, which is a more biologically suitable approach. Despite the acidic character of the cellulose hydrofibre contained in the three dressings, the lack of any antiseptics in the foam forms makes them unsuitable for use in colonised or infected wounds, although they can act as a physical barrier for microorganisms and mechanical damage. The opposite results were observed for the AQUACEL® Ag+Extra dressing, which contains silver, EDTA, and benzethonium chloride. Discussion: Data on the physicochemical composition of dressings can enable healthcare providers to choose the appropriate dressing series to use during wound bed preparation and beyond.

Scientia Pharmaceutica doi: 10.3390/scipharm94030075

Authors: Nyshanbay Konash Jennyfer A. Aldana-Mejía Sebastian John Adams Kumar Katragunta Kiran Kumar Tatapudi Bharathi Avula Ji-Yeong Bae Ikhlas A. Khan Galiya Sayakova Kairat Zhakipbekov Serzhan Mombekov Samir A. Ross

Elymus repens (L.) Gould has a long history of use in traditional medicine across the British Isles, particularly among Gaelic and Anglo-Saxon communities, where it has been employed as a diuretic and anti-inflammatory agent. Despite its ethnopharmacological significance, comprehensive insights into its phytochemical composition and biological activities remain limited. The present study aimed to provide an integrated characterization of E. repens through macro- and microscopic analyses, advanced phytochemical profiling, and evaluation of the biological activities of the rhizome part. Microscopic examination revealed distinct anatomical features differentiating rhizome and stem, leaf tissues, supporting accurate identification and pharmacognostic standardization. Chemical profiling using Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (LC-QToF-MS) enabled the tentative identification of 93 metabolites, including amino acids, in aerial and rhizome extracts. These compounds were primarily classified into polyamines (e.g., feruloylputrescine, hydroxycoumaroylagmatine), phenolic acids (gallic, vanillic, and ferulic acids), flavonoids (apigenin, tricin, saponarin analogues), amino acids (arginine, tyrosine, tryptophan), organic acids (malic, succinic acids), nucleosides (adenosine, thymidine), and phospholipids. Biological evaluation demonstrated that the hydroethanolic rhizome extract exhibited notable antifungal activity against Aspergillus fumigatus (IC50 = 34.9 µg/mL). Additionally, hydroethanolic extracts of both the aerial and rhizome parts showed no cytotoxicity in the Artemia salina lethality assay at concentrations up to 10 mg/mL, indicating a favorable preliminary safety profile. Of particular interest is tricin, which possesses anti-inflammatory, antioxidant, antimicrobial, and potential nephroprotective therapeutic effects; its mechanism of action is associated with the suppression of oxidative stress, the inhibition of pro-inflammatory mediators, and the disruption of metabolic processes in microbial cells. Overall, this study provides a comprehensive phytochemical and pharmacognostic characterization of E. repens, highlighting its potential as a source of bioactive compounds. The metabolite profile obtained directly from the biologically active extract, combined with its proven antifungal activity, serves as direct confirmation of the antimicrobial aspect of this plant’s traditional use, while its broader applications in ethnomedicine require targeted pharmacological testing. These findings contribute valuable data for chemotaxonomic classification and future pharmacological investigations.

Scientia Pharmaceutica doi: 10.3390/scipharm94030074

Authors: Julio Cesar Armenta-Gorosave Gerson Ney Hernández-Acevedo Brenda Chimal-Vega Donato A. Rechy Iruretagoyena Ricardo Delgadillo-Valles José Luis Vique-Sánchez

The World Health Organization (WHO) estimates that by 2050, bacterial resistance will cause 10 million deaths, of which approximately one million are associated with multidrug-resistant (MDR) microorganisms. Staphylococcus aureus is one of the bacteria with high resistance to the most widely used antibiotics that cause infections worldwide. Reports show that approximately 80% of S. aureus strains are resistant to penicillin (methicillin resistance), and that this resistance has been developing since the 1960s (WHO). On the other hand, there are new potential targets to develop new antibiotic drugs; notably, the 3-dehydroquinate dehydratase of S. aureus (SaDHQD) is relevant for this, due to the SaDHQD involved in the metabolism of the S. aureus, which is necessary in the shikimate pathway. This study proposes two compounds against SaDHQD to develop a new antibiotic drug. We performed in silico and in vitro assays for it, and in this way, this study proposes compounds that could be selected against SaDHQD, for the development of a new antibiotic drug.

Scientia Pharmaceutica doi: 10.3390/scipharm94030073

Authors: Rapee Jarungsirawat Chaipat Siriwachirachai Thaned Pongjanyakul

This study aimed to investigate the physical properties of native tapioca starch (TS) ag-glomerated using its gelatinized dispersion as an agglomerating agent and to evaluate the performance of the resulting agglomerate tablets. The results demonstrate that TS agglomerated with gelatinized tapioca starch (GTS) exhibited increased particle strength as GTS content increased. Moreover, particle flowability was enhanced compared with that of native TS. The compressibility of TS agglomerates increased with higher GTS content, thereby reducing resistance to volume reduction and enhancing the plasticity of particle deformation under pressure, resulting in the greater tensile strength of the tablets. GTS showed superior performance to polyvinylpyrrolidone and sodium alginate at the concentration of 2% w/w in terms of Carr’s index and tablet hardness. Propranolol HCl (PNL) tablets prepared from agglomerates with GTS exhibited higher hardness than those without GTS, with tablet hardness increasing proportionally to GTS content. Additionally, GTS facilitated faster tablet disintegration, thereby accelerating PNL dissolution. In drug-loading tests, agglomerate tablets containing 3% GTS maintained acceptable physical properties when the PNL content did not exceed 20% w/w. Higher PNL loading may be achievable by increasing compression pressure. These findings indicate that native TS agglomerated with GTS is a promising tablet diluent for direct compression.

Scientia Pharmaceutica doi: 10.3390/scipharm94030072

Authors: Piyanut Thongphasuk Nuntachai Hanpramukkun Arthimond Vutthiphong Ratana Charoenwattanasatien Phakkhananan Pakawanit Sucharat Limsitthichaikoon

The translation of underutilized botanical resources into advanced therapeutic dosage forms represents a critical frontier in pharmaceutical sciences. This study systematically characterizes the phytochemical and biological profiles of three Acanthus species (Acanthus ebracteatus, Acanthus ilicifolius, and Acanthus montanus) to develop a functional, rapid-release effervescent mouthwash tablet for oral mucosal repair. Phytochemical screening demonstrated that ethanolic extraction selectively concentrated bioactive phenolics and saponins compared to conventional aqueous methods. The ethanolic A. montanus extract emerged as the premier candidate, exhibiting the highest total phenolic content, excellent biocompatibility with human gingival fibroblasts, and significant promotion of in vitro cellular migration. Furthermore, it demonstrated robust, broad-spectrum antimicrobial efficacy against key cariogenic (Streptococcus mutans) and opportunistic (Candida albicans) oral pathogens. To transition this botanical discovery into a viable delivery system, the optimized extract was integrated into an effervescent base via wet granulation utilizing absolute ethanol, followed by blending with extragranular excipients and single-stroke compression. The resulting optimized matrix, incorporating 10% sodium starch glycolate, achieved an ideal mechanical-kinetic balance, yielding exceptional structural toughness (0.23% friability) and rapid disintegration (2.02 min). Advanced 3D synchrotron X-ray tomographic microscopy revealed that this specific super-disintegrant ratio generates a highly interconnected, porous internal architecture driving accelerated capillary-mediated breakdown. Ultimately, this study successfully translates a botanical extract into a mechanistically optimized, functionally validated dosage form for targeted oral therapies.

Scientia Pharmaceutica doi: 10.3390/scipharm94030071

Authors: Christian Goldiș Roxana Racoviceanu Mihaela Jorgovan Roxana Negrea-Ghiulai Codruța Șoica Alexandra Prodea Oana Bătrîna Gabriela Antal Alexandra Mioc

Epilobium parviflorum Schreb. is a medicinal plant used traditionally against inflammatory disorders whose cytotoxic potential is still incompletely revealed. The current study investigates the phytochemical composition and in vitro cytotoxic activity of four hydroalcoholic extracts prepared from the aerial parts of E. parviflorum by using maceration and Soxhlet extraction. The extracts were characterized in terms of total phenolic, flavonoid and tannins composition and LC-MS was used to identify its individual polyphenols. Their biological effects were assessed against four cancer cell lines (A375 melanoma, HT-29 colorectal adenocarcinoma, PANC-1 pancreatic carcinoma and SK-OV-3 ovarian adenocarcinoma cells), while using HaCaT keratinocytes as healthy cells in order to assess selectivity. Cell viability, cytoskeletal and nuclear morphology, mitochondrial respiration and network pharmacology were further investigated. A complex phenolic profile was revealed, with hyperoside being identified as the main component in all extracts while the extraction parameters strongly influenced the recovery of various phenolic compounds. All extracts reduced cancer cell viability in a dose-dependent manner after 24 h exposure, with the most pronounced effects observed at 720 and 1000 μg/mL, while HaCaT cells were left relatively unaffected. The morphological assessment indicated nuclear condensation, fragmentation and cytoskeletal disruption following the application of extracts. Moreover, high-resolution respirometry showed reduced oxidative phosphorylation and electron transfer system capacity thus indicating that early mitochondrial dysfunction may contribute to the cytotoxic effects. Network pharmacology revealed that ERBB2, CTNNB1, HSP90AA1 and HDAC6 might act as molecular targets in melanoma. Thus, these findings support the hypothesis that E. parviflorum hydroalcoholic extracts, particularly the 40% ethanol Soxhlet extract, may serve as important sources of bioactive phytocompounds with antiproliferative and apoptotic properties.

Scientia Pharmaceutica doi: 10.3390/scipharm94030070

Authors: Ayoub El-Mrabet Amal Haoudi Amine Ez-Zoubi Rachid Bouzammit Abdellatif Alami Ahmed Mazzah

Quinoline is a bicyclic aromatic heterocycle composed of a fused benzene and pyridine ring, and it has held an important place in medicinal chemistry for nearly two centuries. F. Runge first isolated it from coal tar in 1834, and it was later found to form the structural core of well-known natural products such as quinine, camptothecin, and γ-fagarine. Its asymmetric electron distribution, amphoteric character, and ability to undergo both electrophilic and nucleophilic substitution confer considerable pharmacophoric versatility on the quinoline scaffold. This review covers the chemistry and therapeutic relevance of quinoline derivatives, with an emphasis on their pharmacological significance rather than on their synthesis alone. It begins with a brief account of the scaffold’s structural features and main synthetic routes, then examines the biological activities reported for quinoline-based compounds, including antibacterial, anticancer, anti-inflammatory, antimalarial, antiparasitic, antitubercular, antioxidant, and antiviral activities, together with structure–activity relationships discussed at the level of specific ligand–target interactions where data allow. The last section covers more recent directions in quinoline-based drug discovery, including PROTAC degraders, kinase inhibitors, and multitarget-directed ligands, an area not extensively addressed in earlier reviews of this scaffold. The literature surveyed here shows that quinoline derivatives continue to serve as a versatile scaffold for generating new leads, linking established synthetic chemistry with current mechanistic and computational approaches. The continued diversification of quinoline-based chemotypes and their biological mechanisms reinforces the importance of this scaffold as a versatile platform for medicinal chemistry and drug discovery.

Scientia Pharmaceutica doi: 10.3390/scipharm94030069

Authors: Yulin Ren A. Douglas Kinghorn

Cytokines are produced by immune and other cells and work as cellular messengers to regulate an immune response and other biological processes. As the main components of the tumor microenvironment (TME), cytokines are involved in the major events of cancer development, including cancer and cancer stem cell proliferation, angiogenesis, invasion, and metastasis. They also modulate immune functions and inhibit tumor progression and resistance to conventional therapies and thus have been regarded as promising targets for cancer treatment. Recently, tumor reversibility has attracted wide interest, for which the TME plays a critical role. Many plant-derived products exhibit potential tumor-inhibitory and cytokine-modulatory activities, including andrographolide, artemisinin, berberine, camptothecin, capsaicin, curcumin, digoxin, morphine, paclitaxel, and vinblastine, indicating their possible use in cancer reversal. Thus, in the present review, correlations among cytokines, the TME, tumor immunity, and tumor reversibility have been discussed, and the potential effects of selected plant-derived natural products on these issues have been addressed.

Scientia Pharmaceutica doi: 10.3390/scipharm94030068

Authors: Hiroyuki Suzuki Yosuke Nishikawa Shurito Odashima Taisuke Konno Ryusuke Ouchi Daisuke Kikuchi Kensuke Usui Kouji Okada Shigeki Kisara Hitoshi Nakamura Yuriko Murai

Risperidone (RIS) oral solution has a bitter taste and is sometimes mixed with beverages to improve palatability and medication adherence. Although the package insert advises against mixing with tea beverages, the effects of beverage type and tea leaf variety on RIS concentration remain unclear. RIS oral solution was mixed with commercially available black tea, green tea, and hojicha beverages, and black tea leaf extracts. RIS concentration in the supernatant was quantified by high-performance liquid chromatography, and its recovery from precipitates was evaluated in selected samples. RIS concentration decreased in all black tea and green tea beverages and black tea extracts, whereas some hojicha beverages showed no significant decrease. The extent of reduction differed among beverage types and black tea leaf varieties. RIS was substantially recovered from precipitates redissolved in methanol or dissolution test fluid 1 (pH 1.2), whereas recovery from dissolution test fluid 2 (pH 6.8) was lower. Chromatographic and UV spectral analyses supported the presence of RIS in redissolved precipitates. The reduction in RIS concentration is associated, at least in part, with transfer into precipitates and depends on beverage type and tea leaf variety. These findings support the recommendation to avoid diluting RIS oral solution with tea beverages.

Scientia Pharmaceutica doi: 10.3390/scipharm94030067

Authors: Șoimița Emiliana Măgerușan Gabriel Hancu Eleonora Mircia

Azelaic acid (AZA) and salicylic acid (SA) are widely used active ingredients in pharmaceutical and cosmetic formulations for the treatment of acne, rosacea, hyperpigmentation, and other dermatological conditions. Despite their frequent co-administration, analytical methods for their simultaneous determination remain limited. In the present study, a capillary electrophoresis (CE) method with indirect UV detection was developed and validated for the simultaneous determination of AZA and SA in pharmaceutical and cosmetic preparations. Preliminary experiments demonstrated that direct UV detection was unsuitable because of the weak UV absorbance of AZA; therefore, indirect UV detection based on a sodium benzoate background electrolyte (BGE) was used. Following an initial one-factor-at-a-time (OFAT) screening, method optimization was performed using a face-centered central composite design (CCD) to evaluate the effects of BGE concentration, BGE pH, and separation voltage on the separation. The optimum separation was achieved using a 30 mM sodium benzoate BGE at pH 6.5 containing 5% (v/v) methanol, a separation voltage of +18 kV, a capillary temperature of 20 °C, and indirect UV detection at 230 nm. Baseline separation of both analytes was achieved within 5 min. The method was validated according to the ICH Q2(R2) guideline and demonstrated satisfactory accuracy, linearity, precision, selectivity, sensitivity, and robustness. The developed procedure was successfully applied to the analysis of commercial cosmetic formulations containing AZA, SA, or both active ingredients, providing assay results consistent with the declared contents. The proposed CE method provides a simple, rapid, cost-effective, and environmentally friendly alternative for the routine quality control of pharmaceutical and cosmetic formulations containing AZA and SA.

Scientia Pharmaceutica doi: 10.3390/scipharm94030066

Authors: Erick Poulsen-Silva María Carolina Otero Diego Verdugo-Igor Gloria González Sofía Díaz-Cornejo Camila Fuentes Maite Rodríguez-Díaz Cristian Atala Felipe Gordillo-Fuenzalida

Mistletoes of the genus Tristerix, native to South America, represent a unique group of mostly hemiparasitic plants with potential medicinal applications. This review synthesizes existing knowledge on their biological and phytochemical properties, focusing on three main species endemic to Chile: Tristerix aphyllus, T. corymbosus, and T. verticillatus. These species exhibit diverse interactions with host plants, animal pollinators, and seed dispersers, where host identity can influence their chemical profile. Around 17 metabolites have been found in flowers, fruits, and leaves from Tristerix spp., including flavonoids (e.g., quercetin, apigenin, luteolin), phenolic acids (e.g., caffeic acid; gallic acid), and alkaloids (e.g., pronuciferine and glaucine). Those have demonstrated antioxidant, anti-inflammatory, antimicrobial, and anti-tumoral properties. Despite their traditional uses in Chilean medicine for ailments such as gastric ulcers and throat infections, experimental research on Tristerix spp. remains scarce. This review highlights their bioactive potential, emphasizing the need for further investigation into their pharmacological applications, including in vivo and clinical studies.

Scientia Pharmaceutica doi: 10.3390/scipharm94030065

Authors: Yuriy Karpenko Volodymyr Parchenko Lyudmila Kucherenko Tetiana Chetvertak Oleksii Bihdan Iryna Pukhalska Olena Roik Daria Safronova Ihor Meladze Inna Bushueva

The matrix metalloproteinases MMP-2 and MMP-9 are involved in extracellular matrix remodeling, inflammatory response, and tissue remodeling, and overactivity of certain metalloproteinases may also contribute to chronic wound healing. The aim of this work was to synthesize novel hybrid derivatives of orotic acid and 1,2,4-triazole and investigate them as potential modulators of MMP-2/MMP-9. The structure of the compounds was confirmed by 1H, 13C NMR spectroscopy, LC–MS, and elemental analysis. Pharmacokinetic properties were calculated using SwissADME, and enzyme interactions were characterized using molecular docking strategies, protein–ligand contact analysis, and 100 ns molecular dynamics. The inhibitory effect was also assessed in vitro by fluorimetry at a concentration of 10 μM. The compounds had an acceptable drug-like profile, without violations of Lipinski’s rule and PAINS warnings. The highest affinity for MMP-9 was also found for the three target proteins 17, 19 and 13, which showed values of −9.65, −9.47 and −9.17 kcal/mol, respectively, compared to −8.37 kcal/mol for NNGH. Dynamic molecular analysis confirmed the stability of the 13–MMP-9 complex. Compounds 17 and 13 inhibited MMP-9 by 94.2 ± 4.8% and 85.2 ± 3.8%, respectively, with little effect on MMP-2, whereas compound 19 showed balanced inhibition of MMP-2 and MMP-9 by 74.2 ± 4.4% and 79.2 ± 2.8%, respectively. The results identified 13 and 17 as potential compounds with preferential effects on MMP-9, and 19 as a possible dual inhibitor for wound healing activity studies.

Scientia Pharmaceutica doi: 10.3390/scipharm94030064

Authors: Getulio Flores-Tlalpa Lenin Domínguez-Ramírez Luis Márquez-Domínguez Julio Reyes-Leyva Paulina Cortés-Hernández Fabiola Domínguez Jesús Hernández Irma Herrera-Camacho Gerardo Santos-López

Although the acute phase of the SARS-CoV-2 pandemic has subsided, the continued emergence of viral variants underscores the need for structurally diverse antiviral inhibitors. In this study, molecular docking followed by molecular dynamics (300 ns) simulations and binding free energy calculations using the Molecular Mechanics Poisson–Boltzmann Surface Area (MM-PBSA) method were employed to evaluate substituted flavonoids derived from Taraxacum officinale and Urtica dioica as potential inhibitors of the SARS-CoV-2 main protease (Mpro/3CLpro). Docking analysis identified several derivatives with favorable binding scores; however, dynamic refinement revealed differential stability among the ligand–protein complexes. Among the evaluated compounds, the luteolin derivative LND-17 showed the most consistent performance, exhibiting binding free energy estimates approaching those obtained for the reference inhibitors nirmatrelvir and ensitrelvir, sustained catalytic pocket occupancy, and energetic contributions involving the catalytic dyad (His41 and Cys145). Additional derivatives, including LNG-04, QND-07, and QNG-20, showed moderate stabilization but lower overall consistency. These findings highlight glycosylated flavonoids as promising scaffolds for future structure-based optimization and provide structural insights to guide experimental validation.

Scientia Pharmaceutica doi: 10.3390/scipharm94030063

Authors: Danil D. Anikev Anastasia Yu. Filippova Olga I. Yarovaya Serafim A. Tishchenko Alla V. Pavlova Alina A. Sonina Kseniya S. Kovaleva Mikhail V. Khvostov Tatyana G. Tolstikova Andrey Yu. Petrov Nariman F. Salakhutdinov

Cridanimod (acridoneacetic acid), the active ingredient of the immunomodulatory drug Cycloferon®, has a well-characterized antiviral profile, but an unexplored analgesic potential. Bornane monoterpenes, notably (+)-camphor and (−)-fenchone, are established scaffolds for analgesic drug design. We therefore synthesized thirteen cridanimod–monoterpene conjugates—seven amides, three acylhydrazones, and three esters—by EDCI/DMAP-mediated coupling or CDI/DBU-promoted esterification, and evaluated them in mice at an oral dose of 10.0 mg/kg in the acetic acid writhing and hot plate tests, with diclofenac sodium (10.0 mg/kg) as the reference. Acridoneacetic acid and Cycloferon® were themselves inactive in both assays. By contrast, six of the thirteen conjugates were significantly active (p < 0.05) in at least one test, with distinct leads in each: amide 19 matched diclofenac in the writhing test (−63.7% vs. −64.4%), whereas acylhydrazone 23 exceeded diclofenac in the hot plate test (+43.9% vs. +25.7%). The divergent profiles suggest that different structural subclasses engage peripheral and central antinociceptive mechanisms. Conjugation thus converts an analgesically inactive immunomodulator into a substance yielding analgesics that match or exceed a standard NSAID at the same oral dose, providing a promising starting point for the development of new pain-relieving agents.

Scientia Pharmaceutica doi: 10.3390/scipharm94030062

Authors: Diana Rodríguez-Vera Eunice D. Farfán-García Elizabeth Estevez-Fregoso Aldo A. Reséndiz-Albor Ivonne Maciel Arciniega-Martínez Eduardo Madrigal-Santillán Jose A. Morales-González Marvin A. Soriano-Ursúa

Morinda citrifolia (Noni) is well known as a plant with therapeutic potential and is also attractive to the food and cosmetic industries. Traditional medicine supports its use, mainly for the treatment of metabolic disorders and chronic inflammation but also for certain types of cancer. Noni has been the subject of considerable interest within the scientific community due to its purported health benefits. However, despite its growing popularity and extensive traditional use, significant gaps remain in the empirical understanding of its properties, mechanisms, and potential applications. To understand its biological activity, particular attention has been given to several chemical compounds present in its leaves and fruits, as they have been identified as bioactive agents. Moreover, several studies support the idea that specific flavonoids and anthraquinones from noni act on enzymes and transporters associated with glucose and lipid metabolism in humans. Its involvement in cardiovascular, neurological, metabolic, and inflammatory regulation across several high-burden diseases expands the potential medical applications of noni. This narrative review presents the current state of knowledge, highlighting preclinical studies that suggest the mechanisms of action underlying the observed effects, including theoretical approaches proposing specific interactions between noni compounds and proteins associated with human diseases as potential therapeutic targets. It also identifies areas where information remains insufficient and proposes future research directions for pharmacological applications, including the need for additional clinical studies and more comprehensive pharmacokinetic and toxicological evaluations.

Scientia Pharmaceutica doi: 10.3390/scipharm94030061

Authors: Sousana K. Papadopoulou Efthymios Poulios Fotis Tsopelas Anna Tsantili-Kakoulidou Constantinos Giaginis

Drug discovery is a complex and resource-intensive process, with lead identification representing a major bottleneck due to high attrition rates. Natural products have long served as a valuable source of structurally diverse and biologically active compounds, offering advantages such as evolutionary optimization, target specificity, and unique chemical diversity. This review provides a comprehensive and mechanistic overview of natural products as lead compounds, emphasizing their chemical characteristics, biological relevance, sources, mechanisms of action, and integration into modern drug discovery pipelines. A narrative review was conducted using major scientific databases (PubMed, Scopus, Web of Science, and Google Scholar), covering literature from 2000 to 2026. Relevant studies were selected based on scientific rigor and contribution to key themes, including natural product diversity, discovery strategies, and technological advancements. Natural products exhibit superior structural complexity and occupy unique chemical space compared to synthetic compounds, enabling effective interaction with diverse biological targets and supporting polypharmacological activity. Key sources include plants, microorganisms, and marine organisms, which have yielded numerous clinically important drugs. Advances in analytical techniques, genome mining, metabolomics, synthetic biology, and artificial intelligence have significantly improved discovery and optimization processes. Despite challenges related to complexity and scalability, natural products remain indispensable in drug discovery, with emerging technologies enhancing their potential for addressing unmet medical needs.

Scientia Pharmaceutica doi: 10.3390/scipharm94030060

Authors: Yakov V. Gorokhov Alexey D. Egorov Nadezhda M. Andriyashina Alexander N. Lobov Irina S. Balashova Aleksandrina S. Volobueva Stanislav A. Grabovsky Sophia S. Borisevich

In this study, we used our own prediction models to assess the antiviral potential of pyrimidin-4(3H)-one derivatives against the A/H1N1 influenza virus strain. This assessment allows us to identify promising structures. The models are based on machine learning algorithms and molecular modeling results. In general, the prediction results are consistent with experimental data. The most promising compound, namely 12 (6-amino-2-(dimethylamino)pyrimidin-4(3H)-one), inhibits the reproduction of the A/Puerto Rico/8/34 (H1N1) influenza virus strain in vitro, likely by affecting the function of the endonuclease domain of the viral polymerase complex. Compound 12 can be used to create new PAN inhibitors by modifying its structure.

Scientia Pharmaceutica doi: 10.3390/scipharm94030059

Authors: Ecaterina Gliga Denisa Gabriela Stroia Gabriel Hancu Eleonora Mircia

Dapagliflozin (DAPA), a selective sodium–glucose cotransporter 2 inhibitor, is widely used in the management of type 2 diabetes mellitus, with additional indications in heart failure and chronic kidney disease. The growing analytical demand for DAPA determination in pharmaceutical formulations, fixed-dose combinations, and biological matrices has stimulated the development of diverse analytical methods. This review provides a comprehensive evaluation of reported techniques for DAPA quantification in different matrices. Approaches discussed include chromatographic methods (TLC, RP-HPLC, UHPLC, LC-MS/MS), electromigration techniques (CE), and spectroscopic methods (UV–Vis, spectrofluorimetry). Emphasis is placed on key performance characteristics such as selectivity, sensitivity, linearity, robustness, and applicability to stability studies and bioanalysis. Recent trends, including the application of Quality by Design, green analytical chemistry principles, and advanced hyphenated techniques, are also addressed. While RP-HPLC remains widely used for routine quality control due to its robustness and accessibility, LC-MS/MS is generally regarded as the method of choice for trace-level bioanalysis owing to its superior sensitivity and selectivity. CE and spectroscopic techniques offer cost-effective and environmentally friendly alternatives, though with certain limitations. This review highlights current methodological gaps and outlines future directions for developing more sensitive and sustainable analytical strategies.

Scientia Pharmaceutica doi: 10.3390/scipharm94030058

Authors: Yulian Voynikov Konstantin Konstantinov Iliyan Ivanov Stanimir Manolov

This review summarizes the synthesis and structural modification of α-pyrone-containing phloroglucinol derivatives from Helichrysum species. Synthetic routes to both natural products and synthetic analogues are covered, highlighting strategies ranging from β-keto ester cyclodehydration to multicomponent condensations. Key methods include aldehyde-mediated dimerization, fluoride-catalyzed heterodimerization, and acid-catalyzed cyclization to benzopyran frameworks. The reported approaches enabled access to diverse monopyrone, dipyrone, arzanol-type, and cyclized analogues. Additionally, retrosynthetic analyses toward phloroglucinol–pyrone heterodimers are discussed, highlighting convergent synthetic strategies for future access to benzofurane-, chromene-, and chromane-based analogues. This review integrates published experimental data with newly generated in silico predictions.

Scientia Pharmaceutica doi: 10.3390/scipharm94030057

Authors: Bhaswati Das Marakanam Srinivasan Umashankar

This study investigates the synergistic therapeutic potential of Rivastigmine (RVG) and Epigallocatechin (EGC) in Alzheimer’s disease (AD), a multifactorial neurodegenerative disorder characterized by neuroinflammation, oxidative stress, and dysregulated signaling pathways. Conventional therapies primarily provide symptomatic relief and target limited pathways, highlighting the need for multi-target strategies with improved efficacy and safety. An integrated in silico approach combining pharmacokinetic evaluation, network pharmacology, molecular docking, and molecular dynamics simulations is used to determine the synergistic potential of RVG and EGC. Pharmacokinetic analysis indicates favorable drug-likeness and acceptable ADME/Tox profiles for both compounds. Network pharmacology identified 146 overlapping targets associated with AD, highlighting key hub genes including NFKB1, MAPK1, STAT1, PRKACA, GRB2, LYN, and PTPN11, which are involved in neuroinflammation, synaptic signaling, and neuronal survival. Functional enrichment analysis indicated significant involvement of MAPK/ERK signaling and immune-regulatory pathways. Importantly, the PD-1/PD-L1 signaling pathway is identified as a novel mechanism connecting neuroimmune modulation with intracellular kinase-driven neurodegeneration. Molecular docking studies showed strong binding affinities of RVG and EGC toward key AD-related targets, particularly MAPK1, supported by stable hydrogen bonding and interaction profiles. Molecular dynamics simulations confirmed stable protein-ligand interactions, with EGC contributing structural stability and RVG exhibiting adaptive flexibility within the binding pocket. These results suggest that the RVG-EGC combination exhibits synergistic potential by simultaneously modulating neuroinflammatory, oxidative stress, and kinase-mediated signaling pathways. The integration of PD-1/PD-L1 and MAPK/ERK signaling provides a novel mechanistic pathway for multi-target therapeutic intervention in AD.

Scientia Pharmaceutica doi: 10.3390/scipharm94030056

Authors: Roman P. Terekhov Maria D. Korochkina Elizaveta V. Krivozubova Grigory Yu. Evzikov Artem A. Svotin Maria N. Anurova Irina A. Selivanova

Oral diseases cause a wide range of difficulties for patients. The natural bioactive compound dihydroquercetin (DHQ), which demonstrates regenerative, anti-inflammatory, antioxidative, and antibacterial effects, is of interest for their treatment. The combination of DHQ and l-lysine DHQ is “very easily soluble”. The aim of this study is to compare orally disintegrating tablets based on raw DHQ and on the DHQ-l-lysine composition. Following the guidelines outlined in the ICH Q8 (R2) standard, a fundamental quality target product profile and critical quality attributes were established. The Sediment Delivery Model (SeDeM) method was used to evaluate the substance suitability for direct compression. Quantitative analysis of the DHQ release was carried out by high-performance liquid chromatography, and infrared (IR) spectroscopy was performed using the attenuated total reflection technique without any prior sample preparation. The DHQ-l-lysine composition shows improved dimensions (4.12) and flowability (4.96). The release rate constants (Krelease) were 8.14 and 3.61%/min, while the half-release periods (t50%) were 6.14 and 13.85 min for tablets with DHQ (TF1) and DHQ-l-lysine compositions (TF2), respectively. The difference factor (f1) and similarity factor (f2) were 23.43% and 43.37%, respectively. The tablet manufacture had a critical impact on the characteristics of the IR spectra (the r values −0.8785 and 0.5474 for TF1 and TF2). The conducted study demonstrates the promise of using DHQ-l-lysine composition for developing effective dosage forms with improved technological characteristics and controlled release of the active substance.

Scientia Pharmaceutica doi: 10.3390/scipharm94030055

Authors: Elena O. Bakhrushina Natalia N. Mikhailova Anastasia N. Golub Ksenia V. Eremeeva Anna-Daniela Koynova Anna A. Popova Andrey B. Goryachev Olga I. Stepanova Ivan I. Krasnyuk Ivan I. Krasnyuk

Acute otitis media is an inflammatory disease affecting all compartments of the middle ear, characterized by localized pain, fever, hearing impairment, and, occasionally, purulent exudate. It represents a significant clinical concern in both pediatric and adult populations, with approximately 709 million cases reported annually worldwide, 51% of which occur in children. However, currently available topical otic formulations are limited by their inability to achieve predictable therapeutic concentrations at the site of inflammation, resulting in reduced efficacy. In addition, the selection of appropriate active pharmaceutical ingredients (APIs) for drug products remains challenging; as a result, existing therapies do not comprehensively address all stages of pathogenesis. This study aimed to analyze existing locally acting formulations for middle ear drug delivery, evaluate their advantages and limitations, and assess modern approaches to the development of novel drug delivery systems and API combinations. A critical review of 69 publications (2010–2026) was conducted, supplemented by a strengths and limitations analysis of dosage forms and an evaluation of APIs based on clinical data. The findings highlight a lack of targeted drug delivery systems, limited efficacy of existing API combinations against bacterial biofilms, and their risk of ototoxicity. Emerging innovative drug delivery approaches, including microemulsions, vesicular systems, stimuli-responsive systems, and hydrogels, have demonstrated promising results in preclinical studies; however, their efficacy and safety remain to be confirmed in clinical settings before their full therapeutic potential in otitis media treatment can be realized.

Scientia Pharmaceutica doi: 10.3390/scipharm94030054

Authors: Kelly del C. Cruz-Salomón Alfredo Briones-Aranda Abumalé Cruz-Salomón Nancy Ruiz-Lau Mariano Martínez-Vázquez Joaquín A. Montes-Molina Gerardo Leyva-Padrón Josue V. Espinosa-Juárez Rosa I. Cruz-Rodríguez

Petiveria alliacea L. (commonly known as “anamu,” “guiné,” “hierba de zorro,” and “tipi”) has been widely used in Mesoamerican traditional medicine to treat pain and inflammation. However, scientific evidence supporting its efficacy in diabetic neuropathy remains limited. This study evaluated the antinociceptive potential of a methanolic leaf extract of P. alliacea in a murine model of alloxan-induced diabetic neuropathy and investigated its possible mechanisms of action. Diabetic CD-1 mice were evaluated for mechanical allodynia and hyperalgesia using the Von Frey test and for tonic pain using the formalin test. Pharmacological antagonists were administered to assess the involvement of opioid, nitric oxide, serotonergic, and GABAergic pathways. Phytochemical profiling was performed by LC-ESI-MS/MS, and potential pharmacological and pharmacokinetic properties of the identified metabolites were predicted using in silico tools (PASS online, SwissTargetPrediction, SwissADME, and pkCSM). The methanolic extract significantly reduced mechanical allodynia and hyperalgesia in diabetic mice and attenuated nociceptive responses in both phases of the formalin test, showing an effect comparable to gabapentin. Antinociceptive activity was not altered by naloxone or L-NAME but was significantly attenuated by methiothepin and bicuculline, suggesting that serotonergic and GABAergic pathways contribute, at least in part, to the observed antinociceptive effects. LC-ESI-MS/MS analysis identified 38 metabolites, including flavonoids, alkaloids, and terpenes, with in silico predictions supporting their potential analgesic and anti-inflammatory activities. The methanolic leaf extract of P. alliacea exhibits significant antinociceptive activity in diabetic neuropathy, partially likely to involve serotonergic and GABAergic mechanisms, supporting its ethnomedicinal use and its potential as a source of novel analgesic agents.

Scientia Pharmaceutica doi: 10.3390/scipharm94030053

Authors: Vivany Maydel Sierra-Sánchez Sergio Adrian Ocampo-Ortega Santiago Villafaña-Hernandez Elvia Mera Jiménez Rolando Alberto Rodríguez Fonseca Asdrubal Aguilera-Méndez Rodrigo Romero-Nava Enrique Hong Martha Edith Macías-Pérez Santiago Villafaña

In triple-negative breast cancer (TNBC), immune checkpoint pathways play a central role in tumor immune evasion. Programmed death protein 1 (PD-1) is an inhibitory receptor expressed on T cells, while its ligand, programmed death-ligand 1 (PD-L1), is commonly expressed on tumor cells and cells within the tumor microenvironment. Their interaction suppresses T-cell activation and promotes immune escape. In this study, we evaluated the potential of small interfering RNA (siRNA) to silence PD-L1 expression in TNBC. Transcriptomic analysis of GEO datasets revealed consistent upregulation of CD274 (PD-L1) in TNBC samples. Three siRNA candidates were designed and evaluated in MDA-MB-231 cells. All siRNAs significantly reduced CD274 expression (>70%), as determined by RT-qPCR. Immunofluorescence analysis confirmed a reduction in PD-L1 protein levels (54.3 vs. 98.7 a.u.), while MTT assays demonstrated preserved cell viability at the working concentration (100 pM), supporting a non-cytotoxic and specific gene-silencing effect. These findings highlight PD-L1 as a viable molecular target and support siRNA-mediated silencing as a promising therapeutic strategy in TNBC.

Scientia Pharmaceutica doi: 10.3390/scipharm94030052

Authors: Chaowalit Monton Poj Kulvanich

Recently, the Quality by Design (QbD) principle has been implemented in the pharmaceutical industry to enhance product and process understanding through a science- and risk-based approach. This study aimed to apply QbD principles to the formulation development of felodipine push–pull osmotic pump (PPOP) capsules. The quality target product profile (QTPP) and critical quality attributes (CQAs) were established. A Box–Behnken experimental design was employed to optimize the formulation variables, including the amounts of Polyox WSR N80, Polyox WSR Coagulant, and sodium chloride, selected based on the initial risk assessment. Four responses were monitored: lag time, release rate and R2 based on zero-order release kinetics, and drug release at 24 h. Results indicated that the optimal formulation consisted of 125 mg Polyox WSR N80, 26 mg Polyox WSR Coagulant, and 30 mg sodium chloride. This formulation met the predefined criteria for lag time (≤6 h) and release kinetics (R2 ≥ 0.95), while drug release at 24 h remained below the target value (≥80%). Because most fitted response surface models were not statistically significant, the generated regression equations and response surfaces were interpreted qualitatively to identify formulation trends rather than as predictive models. Experimental verification showed reasonable consistency in overall response trends, although substantial deviations between predicted and observed values were observed for some responses, particularly drug release at 24 h. Therefore, the present work should be considered a formulation-development and QbD feasibility study rather than a definitive optimization study. These findings demonstrate that the QbD-based approach enabled systematic, multivariate optimization and design space establishment, providing a more structured framework for formulation refinement compared with prior exploratory development and supporting controlled drug release characteristics of felodipine PPOP capsules.

Scientia Pharmaceutica doi: 10.3390/scipharm94020051

Authors: Maykon Jhuly Martins de Paiva Walmirton Bezerra D’Alessandro Iangla Araújo de Melo Damasceno Juliane Farinelli Panontin Taides Tavares dos Santos Sávia Denise Silva Carlotto Herrera Mateus Silva Santos Márcio Trevisan

Flavonoids are a structurally diverse class of plant-derived polyphenolic compounds widely recognized for their pleiotropic biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In oncology, these compounds have demonstrated the ability to modulate key signaling pathways involved in cell proliferation, apoptosis, angiogenesis, and metastasis, highlighting their potential as multitarget therapeutic agents. However, their clinical translation remains significantly limited by unfavorable pharmacokinetic properties, such as poor aqueous solubility, extensive first-pass metabolism, rapid systemic clearance, and consequently low oral bioavailability. In this context, nanotechnology has emerged as a promising strategy to overcome these limitations. This review provides a comprehensive and critical analysis of current nanocarrier-based delivery systems for flavonoids, including polymeric nanoparticles, lipid-based nanocarriers (liposomes, solid lipid nanoparticles, and nanoemulsions), micelles, and cyclodextrin complexes, emphasizing their role in improving drug stability, enhancing cellular uptake, and enabling targeted delivery to tumor tissues through both passive mechanisms, such as the enhanced permeability and retention effect, and active targeting approaches. In addition, recent in vitro and in vivo studies demonstrating the superior antitumor efficacy of nanoencapsulated flavonoids compared to free compounds are discussed. Finally, the major translational challenges, safety considerations, and future perspectives for the clinical application of flavonoid-based nanomedicines in cancer therapy are highlighted.

Scientia Pharmaceutica doi: 10.3390/scipharm94020050

Authors: Avel González-Sánchez Jesús Alfredo Araujo-León Rolffy Ortiz-Andrade Tania Isolina Coral-Martínez Zhelmy Martín-Quintal

This study aimed to determine the absolute bioavailability of quercetin and quantitatively evaluate its pharmacokinetic–pharmacodynamic (PK-PD) relationship regarding acute glucose-lowering effects in normoglycemic and alloxan-induced diabetic rats, addressing whether its in vivo efficacy is driven by the free aglycone or its biotransformed intermediates. Healthy and diabetic rats received single doses of quercetin either orally (75 mg/kg) or intravenously (38 mg/kg). Plasma concentrations of free quercetin were quantified using a validated HPLC-DAD method, and temporal PK-PD relationships between systemic exposure and the percentage variation of glycemia were mathematically evaluated employing Pearson correlation analysis. The absolute bioavailability of free quercetin was significantly impaired by the pathophysiological state, dropping from 59.7% in healthy rats to 40.9% in diabetic subjects. Despite this diminished systemic exposure, oral administration elicited significant hypoglycemic responses. Crucially, the Pearson correlation analysis revealed a pronounced temporal dissociation: the onset of glycemic reduction occurred independently of the maximal circulating concentration of free quercetin. Furthermore, intravenous delivery bypassed first-pass barriers and induced a markedly faster and deeper hypoglycemic effect (up to −47% in diabetic rats). Finally, the diminished bioavailability under diabetic conditions and the stark PK-PD temporal dissociation strongly suggest that quercetin’s acute antihyperglycemic effect is driven by rapid hepatic Phase II biotransformation, implicating conjugated metabolites (rather than the free aglycone) as the principal pharmacological effectors.

Scientia Pharmaceutica doi: 10.3390/scipharm94020049

Authors: Stepan Sysak Wojciech Szczolko Marziyeh Raeispour Malgorzata Kucinska Pawel Bakun Roman Lesyk Philippe Grellier Marek Murias Tomasz Goslinski

Flavone–thiazole–aryl hybrid molecules based on 6-aminoflavone and 5-arylidene-4-aminothiazol-2(5H)-ones were synthesized and subjected to physicochemical and biological studies. Microwave-assisted synthesis was performed in two steps. First, an aminolysis reaction of isorhodanine with 6-aminoflavone was carried out to achieve the corresponding hybrid flavone-thiazole 3, which was later subjected to a Knoevenagel condensation with selected aromatic aldehydes, yielding 5-arylidene derivatives 5a–5i. The resulting hybrids were purified and characterized by UV–Vis, NMR, and HR-MS (ESI). In the UV–Vis spectra of all compounds, two characteristic bands were noted. The UV–Vis spectra in DMF of the studied flavone–thiazole–aryl hybrids consist of two major bands with maxima appearing at 280–288 nm, corresponding to band II and 383–399 nm, corresponding to band I, which clearly distinguish them from the large group of modified flavonoids. Among the compounds tested on human bladder cancer 5637 cells, (5Z)-5-[(4-hydroxyphenyl)methylene]-4-[(4-oxo-2-phenyl-chromen-6-yl)amino]thiazol-2-one (5b) exhibited interesting micromolar activity (IC50 2.37 µM). In addition, four of the tested compounds (3, 5f, 5d, and 5b) presented noteworthy antiplasmodial activity against P. falciparum in the low micromolar range (IC50 1.90–4.90 µM). The obtained group of flavone–thiazole–aryl hybrid molecules constitutes valuable starting points for further structural optimisation, which could usher in future novel active pharmaceutical ingredients and pave the way for novel therapeutic strategies.

Scientia Pharmaceutica doi: 10.3390/scipharm94020048

Authors: Jean Guillon Solène Savrimoutou Patrice Agnamey Vittoria Milano Céline Damiani Luisa Ronga Marie Hanot Sandra Albenque Tshering Zangmo Sarah Monic Noël Pinaud Lindita Lari Mathieu Marchivie Stéphane Moreau Jean-Louis Mergny Serge Moukha Pascale Dozolme Clotilde Boudot Bertrand Courtioux Anita Cohen Pascal Sonnet

A series of substituted pyrrolo[2,3-d]pyrimidines was designed, synthesized, and evaluated in vitro against two protozoan parasites: Plasmodium falciparum and Trypanosoma brucei brucei. Pharmacological studies revealed antiprotozoal activity with IC50 values in the submicromolar to micromolar range. Additionally, the in vitro cytotoxicity of these new compounds was assessed using human HepG2 cells. Among them, the pyrrolopyrimidine derivative 1d emerged as the most potent antimalarial compound, exhibiting a selectivity index (SI) of 600.81 against the P. falciparum chloroquine-resistant W2 strain. For the chloroquine-sensitive 3D7 strain, the most notable selectivity index (SI) was observed for pyrrolo[2,3-d]pyrimidine 1c, with a value of approximately 123. Furthermore, compound 1b demonstrated the most interesting activity against Trypanosoma brucei brucei, with an SI of 39.52, marking it as a promising trypanocidal agent. FRET melting assays confirmed that these nitrogen-containing heterocyclic compounds bind to telomeric G-quadruplexes in P. falciparum and Trypanosoma. However, no clear correlation was found between G-quadruplex binding and antiparasitic activity or selectivity, suggesting that G-quadruplex targeting is unlikely to be the main mechanism underlying cytotoxicity.

Scientia Pharmaceutica doi: 10.3390/scipharm94020047

Authors: Olumayokun A. Olajide Uzeme P. Aluta Emmanuel Mfotie Njoya Hope A. Ogiogio Thomas Hallett

Symptoms of respiratory tract infections (RTI) caused by viral or bacterial triggers include sore throat and cough. Plantago lanceolata (ribwort plantain) is used in herbal medicine to treat symptoms of RTI. This study evaluated the pharmacological actions of P. lanceolata extract (PL) and StrepCough Plantain-Dry cough syrup (PLS) in in vitro models of sore throat and cough. Human tonsil epithelial cells (HTEpiC) cells were stimulated with a combination of lipoteichoic acid and peptidoglycan in the presence or absence of PL or PLS. Levels of TNF-α, IL-6, PGE2, and COX-2 were measured using ELISA, while phospho-p65 protein levels were measured using Lumit® immunoassay. The effects of PL and PLS on bradykinin-induced inflammation and increased intracellular Ca2+ were investigated in bronchial epithelial cells (BEAS-2B), cells over-expressing TRPV1. Results showed that the pre-treatment of HTEpiC cells with PL and PLS resulted in a significant (p < 0.05) reduction in the LTA + PGN-induced increased production of TNFα, IL-6, PGE2, as well as COX-2 and phospho-p65 protein levels. Bradykinin-induced increased levels of TNFα, IL-6, and PGE2 in BEAS-2B cells over-expressing TRPV1 were also reduced by PL and PLS, while reducing levels of intracellular Ca2+. This study has demonstrated that extract of P. lanceolata and StrepCough Plantain-Dry cough syrup reduce inflammation in human tonsil epithelial cells. The extract and syrup also reduced TRPV1-mediated inflammation and increased intracellular Ca2+ in BEAS-2B bronchial epithelial cells. This study has provided pharmacological evidence for the use of P. lanceolata in healthcare interventions to treat symptoms of respiratory tract infection.

Scientia Pharmaceutica doi: 10.3390/scipharm94020046

Authors: Zinah K. Al-Qaysi Ali A. Al-Kinani Raid G. Alany

The cornea and conjunctiva are particularly susceptible to injury and adverse effects, either induced by topically applied drugs or excipients used in ophthalmic formulations. Surfactants and cosurfactants are important for producing topical eye formulations of poorly water-soluble drugs, yet they have not been always used in concentrations that are nontoxic and non-irritating to the ocular surface. This study systematically compared the cytotoxicity and ocular irritation potential of commonly used ophthalmic surfactants and cosurfactants under standardized experimental conditions using complementary in vitro and ex vivo ocular safety models. The ocular irritation of Tween 80, Cremophor EL, polyethylene glycol 400 (PEG 400) and propylene glycol (PG) was examined using the HET-CAM (conjunctival) and BCOP (corneal) eye assays. The toxic effect of the four excipients after 24 h on HLE-B3 cell growth was investigated and found to be dose-dependent. The highest tolerable concentrations of Tween 80 and Cremophor EL were 0.25% (w/w), whereas PEG 400 and PG were non-toxic at 5% (w/w). Tween 80 and Cremophor EL at 0.25% (w/w) and PEG 400 and PG at 5% (w/w) were all devoid of conjunctival and corneal irritation. This study systematically compared the cytotoxicity and ocular irritation potential of commonly used ophthalmic surfactants and cosurfactants under standardized experimental conditions using complementary in vitro and ex vivo ocular safety models. Interestingly, there is strong agreement between the results obtained using the HET-CAM and BCOP assays, where both have been successfully used to evaluate the potential for ocular irritation caused by the aforementioned excipients.

Scientia Pharmaceutica doi: 10.3390/scipharm94020045

Authors: Alexander Gerasimov Dar’ya Khabibulina Liana Zubaidullina Elina Mirgazieva Nikolay Lyadov Ruslan Nagrimanov Semen Lapuk

Obtaining amorphous forms of drugs is one of the ways to increase bioavailability. This is especially important for active pharmaceutical ingredients belonging to class II and IV according to the biopharmaceutical classification. These compounds include the currently widely used fluoroquinolone antibiotics. They have low solubility in water and are therefore typically used as hydrochlorides. The presence of a strong acid and a charged active pharmaceutical ingredient in the drug increases solubility, but can also lead to additional side effects and decreased permeability. One way to improve the properties of active pharmaceutical ingredients is to convert them to amorphous form. In this study, an amorphous form of the fluoroquinolone antibiotic norfloxacin was obtained, its stability was determined, and its solubility was studied. It was shown that the resulting amorphous form has good temporal stability. The optimal models describing the cold crystallization process are the Nakamura and Sbirrazzuoli models. Despite the slower dissolution kinetics compared to the crystalline sample, the amorphous form shows higher equilibrium solubility values. These results can be used in pharmaceutical engineering to produce amorphous forms of active pharmaceutical ingredients and determine their stability.

Scientia Pharmaceutica doi: 10.3390/scipharm94020044

Authors: Mounishwaran Kamalesan Mohanraj Raja Rameshkumar Neelamegam Muthukalingan Krishnan Kayalvizhi Nagarajan Douglas J. H. Shyu

Green synthesis of silver nanoparticles (CP-AgNPs) using Calotropis procera (CP) offers a sustainable approach to producing multifunctional therapeutic nanomaterials. This study aimed to synthesize CP-AgNPs and evaluate their antimicrobial, antioxidant, anti-inflammatory, and anticancer potential, with a focus on Helicobacter pylori and gastric cancer cells. CP-AgNPs were prepared by phytochemical reduction using CP leaf extract and characterized by UV–Vis, XRD, FTIR, SEM, EDX, TEM, and Zeta. Antibacterial activity against H. pylori, time-kill kinetics, and SEM imaging of membrane damage were performed. Antioxidant (DPPH, ABTS) and anti-inflammatory assays, together with cytotoxicity studies in AGS cells (DAPI, AO/EtBr, and SEM), were also conducted. CP-AgNPs exhibited an SPR peak at 432 nm, face-centered cubic crystallinity, and spherical morphology (8–32 nm). They showed strong, dose-dependent antibacterial activity against H. pylori, surpassing metronidazole at higher doses. Time-kill assays and SEM confirmed membrane disruption. Antioxidant activity was notable (IC50: 40 µg/mL for DPPH; 60 µg/mL for ABTS). CP-AgNPs demonstrated significant anti-inflammatory effects and dose-dependent cytotoxicity in AGS cells, inducing apoptosis and morphological alterations. The broad biological activity of CP-AgNPs likely arises from the synergy between silver ions and CP phytochemicals. Their superior antibacterial effects, combined with antioxidant and anti-inflammatory properties, indicate strong therapeutic potential for gastric diseases. Anticancer activity in AGS cells suggests additional biomedical relevance, which may involve ROS-associated and apoptosis-related pathways, as suggested by previous studies. CP-AgNPs represent a promising natural nanoplatform for managing H. pylori infection, oxidative stress, inflammation, and gastric cancer, warranting further mechanistic and in vivo studies.

Scientia Pharmaceutica doi: 10.3390/scipharm94020043

Authors: Miguel Ernesto Guzmán-Rodríguez Marco Antonio Valdez-Flores Cinthia Ayón-Fernandez José Juan Ordaz-Ortiz Alma Marlene Guadrón-Llanos Javier Magaña-Gómez Alberto Kousuke de la Herrán-Arita Josué Camberos-Barraza Verónica Judith Picos-Cárdenas Juan Fidel Osuna-Ramos Claudia Desireé Norzagaray-Valenzuela Loranda Calderón-Zamora

Hypertension remains a leading cause of global morbidity and mortality, and angiotensin-converting enzyme (ACE) represents a central therapeutic target within the renin–angiotensin–aldosterone system. Marine microalgae, particularly Phaeodactylum tricornutum, provide an underexplored reservoir of structurally diverse metabolites with potential cardiovascular relevance. In this in silico study, we characterized metabolites putatively annotated by UPLC-ESI-HRMS and evaluated their predicted ACE inhibitory potential. We performed molecular docking with AutoDock 4 and assessed pharmacokinetic and toxicological properties using the SwissADME, PASS, and ProTox platforms. Several metabolites showed favorable binding orientations within the ACE catalytic pocket, including interactions with key residues and proximity to the zinc-binding motif. Lehualide G, Val–Asn–Pro, tanariflavanone B, hydroxyterbinafine, and anhydro-vitamin A exhibited the most favorable docking profiles. PASS predictions indicated vascular-related bioactivity signals for selected compounds, whereas ADMET modeling revealed heterogeneous but classifiable pharmacokinetic and safety characteristics. The convergence of predicted binding compatibility, bioactivity signals, and stratified safety margins supports P. tricornutum as a promising source of candidate molecules for further experimental validation in antihypertensive research.

Scientia Pharmaceutica doi: 10.3390/scipharm94020042

Authors: Athip Maha Thanapat Songsak Surang Leelawat Chaowalit Monton

The present study aimed to establish a robustness modeling framework for the determination of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) in cannabis extract using a multivariate approach. A two-level full factorial design was implemented to examine four critical analytical factors, including methanol concentration (80–85% v/v), flow rate (0.8–1.2 mL/min), column temperature (23–27 °C), and detection wavelength (208–212 nm). Seven analytical responses for each compound were assessed, including peak area, retention time, resolution, asymmetry factor, number of theoretical plates, capacity factor, and peak area difference relative to the reference method. Statistical analysis demonstrated that both main effects and interaction effects significantly influenced the measured responses. Design space construction was performed based on predefined acceptance criteria to ensure method robustness: resolution > 1.5, asymmetry < 1.5, number of theoretical plates > 2000, capacity factor > 2, and peak area difference within −5% to 5%. Predictive performance of the developed models was verified by comparing predicted and experimental results. Good agreement was observed under most conditions, whereas deviation was noted for THC quantification at a detection wavelength of 212 nm. Furthermore, CBD and THC contents determined under three selected operating conditions within the established design space were statistically comparable to those obtained using the reference method, except for the condition employing 212 nm detection. The Analytical GREEnness Metric Approach (AGREE) assessment indicated moderate greenness performance of the analytical procedure. Overall, the multivariate two-level full factorial design proved to be an effective tool for robustness modeling of the HPLC method for simultaneous quantification of CBD and THC.

Scientia Pharmaceutica doi: 10.3390/scipharm94020041

Authors: Liliia Vyshnevska Maryana Yaromiy Iryna Pestun Kaloyan D. Georgiev Iliya Zhelev Slavov Oleh Koshovyi

The pharmaceutical development of cannabis-based medicinal products is challenged by significant variability in the quality, composition, and standardization of plant-derived active pharmaceutical ingredients (APIs). In Ukraine, despite recent legislative liberalization, a substantial shortage of standardized raw materials continues to limit the development of innovative dosage forms. This study analyses international practices among API manufacturers to identify technological parameters necessary to overcome domestic market barriers and support the implementation of advanced drug delivery systems. Content analysis was conducted on regulatory documentation, professional literature, and manufacturers’ technical specifications. Candidate evaluation followed predefined inclusion and exclusion criteria. The study assessed compliance with Good Manufacturing Practice (GMP) requirements, extraction and purification technologies, the extent of analytical characterization, and batch-to-batch reproducibility. Purposive sampling enabled a comparative analysis of various technological approaches. Marked heterogeneity was observed in API standardization and analytical control indicators among manufacturers. Possession of a GMP certificate was found necessary but may be insufficient to ensure the pharmaceutical equivalence of materials. Differences in extraction methods and purification levels may affect stability profiles, pharmaceutical development strategies, and risk management related to final product quality. The findings demonstrate that manufacturer selection is a critical decision point in pharmaceutical development, with substantiated supplier choice directly influencing dosage form development and regulatory compliance.

Scientia Pharmaceutica doi: 10.3390/scipharm94020040

Authors: Sreenivas Avula Satish Koppireddi Micky D. Tortorella Cleopatra Neagoie

Thiazolyl-benzene/camphor sulfonamide derivatives (series 4a–k, 5a–j and 6a–i) were synthesized by reaction of various aryl sulfonyl chlorides and camphor sulfonyl chlorides with 2-amino-4-phenylthiazole. The compounds were evaluated for antibacterial, antioxidant, and α-glucosidase/α-amylase inhibitory activities. Biological screening showed that 4h, 5g and 5i displayed significant activity against most Gram-positive bacteria (MICs 4.68–18.75 µg/mL), while 4b and 5i were active against most Gram-negative bacteria with similar MIC ranges. In the DPPH assay, 4e, 4f, 4g and 4h exhibited slightly stronger radical-scavenging activity than ascorbic acid (IC50 ≈ 3.5–3.8 µM vs. 4.14 µM); 5f emerged as the best dual carbohydrate-digesting enzyme inhibitor, and 5b and 5e demonstrated selectivity toward α-amylase.

Scientia Pharmaceutica doi: 10.3390/scipharm94020039

Authors: Sakthidhasan Periasamy Rajesh Ramasamy Rajasekar Chinnaiyan Arun Sridhar

Background/Objectives: Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health challenge, exacerbated by the emergence of multidrug-resistant strains and limited efficacy of existing therapies. Given the involvement of multiple essential mycobacterial proteins, multitarget drug discovery represents a rational therapeutic strategy. Methods: In this study, an integrated in silico pipeline combining machine learning–based quantitative structure–activity relationship modeling, graph neural network–driven drug–target affinity prediction, molecular docking, molecular dynamics (MD) simulations, and pharmacokinetic–toxicity profiling was employed to identify potential antitubercular leads from natural products. Results: A curated library of over 0.69 million compounds from the COCONUT database was systematically screened against seven essential M. tuberculosis protein targets. Machine learning and heterogeneous graph neural network models effectively captured complex ligand–protein interaction patterns, enabling high-confidence multitarget prioritization. Structure-based docking and MM-GBSA analyses revealed favorable binding affinities, further supported by 100 ns Molecular Dynamics simulations demonstrating stable binding and conformational integrity. In silico ADMET and toxicity predictions identified pharmacokinetically balanced candidates, while density functional theory calculations corroborated favorable electronic properties. Conclusions: Notably, a myricetin-based flavonoid glycoside exhibited consistent multitarget binding and dynamic stability across all targets. Overall, this study underscores the potential of integrated artificial intelligence and structure-based approaches in accelerating natural product-based antitubercular drug discovery and supports further experimental validation of prioritized leads.

Scientia Pharmaceutica doi: 10.3390/scipharm94020038

Authors: Ayşe Türkdoğan Tarek Alloush Burcu Demiralp

Historically, pharmaceutical formulation development relied heavily on trial-and-error experimentation, which was useful for empirical progress but often provided limited mechanistic understanding and insufficient efficiency for increasingly complex drug products. The introduction of Design of Experiments (DoE) and Quality by Design (QbD) established a more systematic framework for studying formulation variables, manufacturing parameters, and Critical Quality Attributes (CQAs). Approaches such as factorial designs, response-surface methodology, and mixture designs have therefore become central to modern pharmaceutical development because they improve experimental efficiency and support the definition of design space. However, as formulations become more nonlinear, high-dimensional, and multi-objective, these classical approaches may no longer be sufficient on their own. This review examines the evolution of experimental design in pharmaceutical research, from one-factor-at-a-time experimentation to structured DoE/QbD strategies, and then to emerging intelligent optimization methods. Its central objective is to clarify when conventional DoE/QbD remains appropriate and when it should be complemented by machine learning, Bayesian optimization, digital twins, and closed-loop experimental systems. The review first summarizes the foundations and strengths of classical experimental design; then, it discusses its practical limitations in complex formulation settings, and finally evaluates how data-driven and hybrid approaches can extend pharmaceutical development. Evidence from tablets, capsules, nanocarriers, transdermal patches, and biotherapeutic systems suggests that intelligent optimization can improve predictive performance and experimental efficiency when used alongside, rather than instead of, established pharmaceutical development principles.

Scientia Pharmaceutica doi: 10.3390/scipharm94020037

Authors: Maksim E. Mironov Dmitry S. Baev Mohammad S. Hamad Sergey A. Borisov Vyacheslav I. Krasnov Tatyana V. Rybalova Maksim P. Pitukhin Irina V. Sorokina Tatyana G. Tolstikova Andrey G. Pokrovsky Anastasia I. Poltanovich Elvira E. Shults

Alkyn-1,2-diones have gained great attention as useful building blocks in organic synthesis. Regioselective synthetic routes towards 3,5-disubstituted isoxazoles, containing the methylfuroyl or diterpenylfuroyl moiety at the C-3 or C-5 position from alkyne-1,2-diones 1, 2, 3, are reported. The reaction with hydroxylamine hydrochloride 6 in ethanol afforded the 1,2-addition products: 5-aryl-3-(methylfuran-2-carbonyl)isoxazoles (yield 61–94%) or 16-(5-arylisoxazole-3-carbonyl)labdatrienes (yield 48–97%). The reaction of alkynediones 1–3 with 6 in THF in the presence of triethylamine led to 5-hydroxy-4,5-dihydroisoxazoles and subsequent dehydration afforded regioisomeric 3-aryl-5-(methylfuran-2-carbonyl)isoxazoles or 16-(3-arylisoxazole-5-carbonyl)labda-trienes (yield 65–98%). New heterocyclic compounds exhibited significant analgesic action in acetic acid writhing and hot-plate tests, and the activity was comparable to reference drugs diclofenac sodium and celecoxib. Isoxazoles, which possessed the most analgesic activity, reduced the concanavalin A-induced inflammation by 34–51%; the effect was comparable to the drug indomethacin. The results of in vitro biological assays (MTT test) revealed that isoxazoles were non-toxic against the normal epithelial VERO cells, and 16-(3-aryl-5-hydroxyisoxazoline-5-carbonyl)labdatrienes 20–24 exhibited selective cytotoxicity against the breast adenocarcinoma MCF 7 (GI50 = 4.7–8.3 μM) and cervical cancer cells C33 A (GI50 = 3.4–4.7 μM). Molecular docking analysis to determine the binding potential of new molecules to the active site of human COX-1 and COX-2 enzymes was conducted.

Scientia Pharmaceutica doi: 10.3390/scipharm94020036

Authors: Feiyun Wang Jing Hao Mengjie Li Yuying Zhu Jiange Zhang

Qin Bing eye drops, a traditional Chinese medicine-based in-hospital preparation, were historically indicated for the treatment of conjunctivitis, keratitis, and photokeratitis. This study aimed to develop Qin Pi extract (QP-E) using a proprietary extraction method, and to evaluate the therapeutic efficacy of QP-E alone, QP-E combined with Bing Pian (BP), and an ophthalmic formulation (QP-D) comprising both constituents in a preclinical model of dry eye disease (DED). DED was induced in mice via subcutaneous scopolamine administration alone, whereas a more robust dry eye phenotype was established in rats through combined treatment with scopolamine and environmental stressors. Ocular surface evaluation included measurement of tear secretion volume and corneal fluorescein staining scores. The results demonstrated that both QP-E monotherapy and the QP-E–BP combination significantly ameliorated key pathological features of DED, including tear film instability and corneal epithelial damage. QP-D—formulated with rationally optimized concentrations of QP-E and BP—significantly enhanced basal tear secretion and attenuated corneal epithelial injury in both murine and rat dry eye models. Mechanistic investigations revealed that QP-E treatment markedly inhibited VEGF-C secretion from classically activated (M1) macrophages, suppressed phosphorylation-dependent activation of the VEGF-C/VEGFR-3 signaling axis, and consequently impaired lymphatic endothelial cell migration and in vitro tube formation. These correlative findings indicate that QP-E may partially alleviate DED by suppressing lymphangiogenesis; however, direct causal evidence—such as genetic ablation of VEGF-C or pharmacological inhibition of VEGFR-3—was not established in the present study. Collectively, our data yield a testable mechanistic hypothesis and propose a novel therapeutic strategy targeting lymphatic remodeling for DED intervention.

Scientia Pharmaceutica doi: 10.3390/scipharm94020035

Authors: Adama Peña-Vera Sandra Dévora-Gutiérrez Chaxiraxi Morales Marrero Isabel V. Figueiredo Susana Abdala Kuri

Adverse Drug Reactions (ADRs) represent a major public health concern due to their impact on patient safety. In Spain, the Spanish Agency of Medicines and Medical Devices, through the FEDRA database, coordinates the reporting of suspected ADRs under real-world conditions of use, contributing to the continuous updating of safety information. In this context, community pharmacist, through Professional Pharmaceutical Care Services, plays a key role in the early detection of ADRs and Drug-Related Problems (DRPs). This article describes the case of a 70-year-old polymedicated woman included in a Personalized Dosage System (PDS). Following the substitution of diazepam with clonazepam and an increase in the dose of semaglutide, the patient developed urinary incontinence, nausea and abdominal pain. Coordinated intervention between the community pharmacy and primary care enabled adjustment of the clonazepam dose, optimization of semaglutide administration and discontinuation of unnecessary naproxen use. These measures resulted in improved treatment tolerance and safety, as well as optimization of pharmacotherapy.

Scientia Pharmaceutica doi: 10.3390/scipharm94020034

Authors: Akira Kageyama Takahiko Aoyama Rikuya Maehara Dai Harada Takashi Kawakubo Yasuhiro Tsuji

The usefulness of ChatGPT, a large language model, has recently been explored in medical research. However, no studies have examined its reproducibility or applicability to therapeutic drug monitoring (TDM), a core task of clinical pharmacists. In this simulation study, we evaluated the feasibility of using ChatGPT for vancomycin (VCM) TDM based on Bayesian estimation. A total of 1000 virtual patients were generated by Monte Carlo simulations using a population pharmacokinetic model of VCM. Bayesian-estimated pharmacokinetic parameters and predicted concentrations were input into ChatGPT, and dosage regimens were compared among the three conditions, using temperature as a hyperparameter (T = 0.1, 0.5, and 1.0). Reproducibility was evaluated using the mode percentage in repeated runs. The reproducibility of the ChatGPT output was higher at T = 0.1 than at T = 0.5 and T = 1.0. When ChatGPT simulated the mode-recommended regimen (T = 0.1), the target attainment rate of the area under the serum concentration (AUC) (400–600 mg·h/L) improved from 25.5% (pre-optimization AUC (fixed-dose regimen)) to 71.5% (post-optimization AUC (ChatGPT-guided regimen)). These findings demonstrate that ChatGPT-based TDM using Bayesian estimation can enhance dose optimization. Adjusting the hyperparameter temperature to 0.1 improved reproducibility, suggesting that a reliable ChatGPT-assisted TDM support system may be clinically useful.

Scientia Pharmaceutica doi: 10.3390/scipharm94020033

Authors: Valmik Sopan Aware Shreya Rajesh Rao Sanjay Pundalik Khairnar Arati Prabhu Hetal Abhay Shah Sonal M. Manohar

Background: Cancer is a leading cause of mortality worldwide. Discovery of small molecules as anticancer agents is an active area of research, as these molecules possess the remarkable ability to interact with specific targets within cancer cells. Objectives: In vitro anticancer activity of six hit derivatives from a series of 2-phenyl-substituted 4-amino–6, 7-dihydro-5H-cyclopenta[d]pyrimidines was tested against human cancer cell lines, viz., A549 (human lung cancer) and A431 (human skin cancer). Methods: Cytotoxicity was evaluated for six hits by the standard MTT assay. Further, their effect on clonogenic potential and cell cycle was tested using colony forming assay and flow cytometric analysis, respectively. Apoptosis-inducing potential was confirmed using Caspase-3/7 Glo assay and detection of cleaved caspase-3 by immunofluorescence. The effect on cell migration was tested using a wound healing assay. Target analysis, Molecular docking and ADMET simulations were performed to identify molecular targets, interactions and assess pharmacokinetic profiles. Results: Specific derivatives showed good to moderate cytotoxicity against A549 and A431 (with average IC50 in the range of ~30 µM), and these hits led to apoptosis and G1 arrest in these cell lines, respectively. Furthermore, identified hits inhibited cell migration in A549 cells. Computational consensus target analysis identified EGFR and CDK2 as high-confidence targets. Docking studies indicated favorable interactions and stability, whereas the ADMET analysis confirmed the drug-likeness and optimal pharmacokinetic and safety profiles of the small molecules. Conclusions: Our current study demonstrates the anticancer potential of novel pyrimidine derivatives. We envisage the use of these small molecules as promising anticancer agents, particularly in skin and non-small cell lung cancer.

Scientia Pharmaceutica doi: 10.3390/scipharm94020032

Authors: Sajib Chandra Roy Md. Jahid Hossain Uttom Kumar Sreedam Chandra Das Fatema Moni Deepankar Sutradhar Faria Tasneem A. S. M. Monjur Al Hossain

Improving the dissolution and solubility of poorly water-soluble drugs remains a major challenge in drug development. Solid dispersion (SD) techniques offer an effective strategy by which to enhance the bioavailability of BCS Class II drugs such as ivermectin (IVM). This study aimed to develop and validate stability-indicating analytical methods for the quantification of IVM and to evaluate the performance of the formulated SDs. A novel RP-HPLC and a UV spectrophotometric method were developed and validated in accordance with ICH guidelines. IVM SDs were prepared via physical mixing (PM), solvent evaporation (SE), and melt fusion (MF) using Poloxamer 188, Kollicoat® IR, and PEG 6000 at respective ratios of 1:1, 1:3, and 1:5. Dissolution studies showed a marked enhancement in drug release from SDs prepared by SE and MF methods compared with pure IVM. Among all formulations, the Poloxamer 188-based binary SD prepared by the SE method at a 1:5 ratio exhibited the highest dissolution (98.55% at 60 min), with release kinetics following anomalous (non-Fickian) transport (n = 0.681) according to the Korsmeyer–Peppas model. Solid-state characterization evidenced by FTIR, DSC, TGA, and SEM confirmed the transformation of IVM from its crystalline form to an amorphous state. Future studies will focus on the in vivo evaluation of the optimized IVM SD formulations.

Scientia Pharmaceutica doi: 10.3390/scipharm94020031

Authors: Regina Julieta Delgadillo Hernández Gregorio Guadalupe Carbajal Arízaga José Alfonso Cruz Ramos Rodolfo Hernández Gutiérrez José Armando Hernández Díaz Ana Alejandra Arias García Norma Morales-Hernández José Nabor Haro-González Zaira Yunuen García Carvajal Moisés Martínez Velázquez

This research aimed to develop glycerol–gelatin vaginal suppositories loaded with melatonin to enhance the localized effects of antineoplastic agents. The solubility of melatonin in different solvents was determined, and glycofurol, which is approved for pharmaceutical use, presented the highest solubilizing capacity. Furthermore, the cytotoxicity of melatonin incorporated into suppositories against HeLa cells was evaluated using MTT assays, individually and in combination with cisplatin. The results indicate that melatonin enhances the cytotoxic effects of cisplatin. The optimal formulation obtained from an experimental design was 33% gelatin, 1% PVA, 1% PEG 6000, 10% glycerol, 15% glycofurol, and 40% water. To ensure that the vaginal suppositories presented the necessary physical properties for optimal handling and application, tests were performed to determine weight uniformity, texture, surface features and disintegration time. Vaginal suppositories weighted around 1.43 g, showed Young’s modulus values of 7389.6 N/m2 and hardness around 1100 gf, and they disintegrated after 30 min at pH 4.2. Additionally, for in vitro melatonin release, FTIR and XRD tests confirmed the presence of melatonin in the formulation. It is concluded that the developed vaginal suppositories can be explored as potential vehicles for localized delivery of melatonin to the tumor site to enhance therapeutic outcomes.

Scientia Pharmaceutica doi: 10.3390/scipharm94020030

Authors: Maryna Stasevych Mykhailo Hoidyk Viktor Zvarych Andriy Karkhut Svyatoslav Polovkovych Roman Lesyk

The development of novel antiepileptic agents requires early identification of pharmacokinetic limitations to mitigate risks at later stages. This study aimed to perform in silico profiling of a library containing 448 novel 2H,5H-chromeno[4’,3’:4,5]thiopyrano[2,3-d]thiazol-2-one derivatives to select lead compounds with an optimal balance of safety and efficacy. The study was conducted using the ADMET-AI platform, based on a graph neural network, to predict physicochemical, pharmacokinetic, and toxicological properties. The methodology involved calculating drug-likeness descriptors for primary screening and a comparative statistical analysis of the top 20 selected structures against 16 approved antiepileptic drugs and four reference compounds. Based on drug-likeness descriptors and predicted ADMET (absorption, distribution, metabolism, excretion, toxicity) related parameters, 20 structures were prioritized for further analysis. Their predicted profiles suggested high intestinal absorption and blood–brain barrier (BBB) permeability, which may be relevant for central nervous system (CNS) directed agents. In comparison with the reference thiazolidinones, the prioritized compounds showed comparatively more favorable predicted mutagenicity and carcinogenicity profiles. Elevated predicted risks of hepatotoxicity and cardiotoxicity were observed for several structures, indicating the need for further structural optimization. The results suggest that the thiopyranothiazolidinone scaffold merits further anticonvulsant-oriented investigation at the stage of early compound prioritization. Experimental validation will be required to confirm the actual pharmacokinetic, toxicological, and anticonvulsant properties of the prioritized compounds.

Scientia Pharmaceutica doi: 10.3390/scipharm94020029

Authors: Rita I. L. Catarino Maria Fernanda C. Leal Adriana M. Pimenta Maria Renata S. Souto Francisco A. M. Silva

Taxanes, such as paclitaxel and docetaxel, are microtubule-stabilizing agents widely used in oncology, either as monotherapy or in combination regimens. While highly effective, these first-generation taxanes face important limitations, including significant toxicity, reduced water solubility, and the emergence of multidrug resistance. To address these challenges, semi-synthetic taxoids have been developed, aiming to improve pharmacological profiles and overcome therapeutic barriers. Central to these efforts is the understanding of structure-activity relationships, which guides the rational design of taxane analogues with enhanced efficacy and safety. This review explores recent advances in taxoid development, highlights findings from clinical trials, and evaluates how these new agents compare with traditional taxanes in terms of therapeutic potential and tolerability. While novel delivery systems offer improved outcomes with existing drugs, the development of new taxane analogues remains a promising approach to address drug resistance, albeit with challenges related to toxicity, high costs, and historically low success rates in drug development. Furthermore, taxanes are already used in certain cardiovascular conditions and show emerging potential in neurodegenerative diseases, although current evidence remains largely limited to preclinical or early-phase clinical studies. These developments mark an important evolution in the field and offer new opportunities for future therapeutic strategies.

Scientia Pharmaceutica doi: 10.3390/scipharm94020028

Authors: Samia Farhaj Omar Hamid Noman Ahmad Barbara R. Conway Muhammad Usman Ghori

Children are often underserved by adult-oriented oral medicines, leading to off-label use and dosage-form manipulation that may compromise dosing accuracy. This review summarises recent advances in paediatric orodispersible tablets (ODTs), focusing on manufacturing technologies, superdisintegrants, taste masking, and in vitro disintegration testing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance and a protocol registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (registration number INPLASY2025110022), we searched PubMed, EMBASE, MEDLINE, Scopus, and Google Scholar for experimental studies on paediatric-relevant ODT formulation and evaluation. Two reviewers screened studies and extracted data on manufacturing methods, excipients, disintegration/dissolution testing, and key outcomes. Risk of bias was assessed using a six-domain framework. Overall, 65 studies met the inclusion criteria for this review. Direct compression was the dominant method, with freeze-drying, sublimation, spray-drying, nanoparticle-in-tablet systems, and semi-solid extrusion/3D printing also reported. Crospovidone, croscarmellose sodium, and sodium starch glycolate were the most common superdisintegrants, while natural and co-processed disintegrants showed promise as cost-effective alternatives. Disintegration was usually assessed using pharmacopoeial methods, with some modified set-ups to better simulate oral conditions. Paediatric ODT development is advancing rapidly. Broader translation requires harmonised disintegration testing, age-stratified acceptability reporting, and GMP-ready workflows, alongside benchmarking of superdisintegrants and attention to dose flexibility, packaging, and affordability.

Scientia Pharmaceutica doi: 10.3390/scipharm94020027

Authors: Cecilia Guadalupe de Loza-García Ana Belem Rubio-García Salvador Hernández-Estrada Luis Alfonso Hernández-Villaseñor Luis Antonio Ramirez-Contreras Jorge Manuel Silva-Jara Jorge L. Mejía-Méndez Zuamí Villagrán Eugenio Sánchez-Arreola Napoleón González-Silva Luis Miguel Anaya-Esparza

Kalanchoe daigremontiana, a succulent herbaceous plant in the Crassulaceae family from Madagascar, has gained global popularity as an ornamental and medicinal species. This review examines the traditional uses, phytochemical composition, biological properties, toxicological aspects, and regulatory challenges of K. daigremontiana. The traditional medicinal uses of its leaves and roots include treating burns, rheumatic disorders, hypertension, diabetes, kidney pain, diarrhea, cough, fever, gastric issues, anxiety, inflammation, and cancer. Chemical compounds identified include phenolic acids, flavonoids, tannins, alkaloids, glycosides, saponins, sterols, terpenes, and fatty acids, with phenolic compounds and bufadienolides being predominant. In vitro studies of the crude extracts, bufadienolide-rich fractions, and isolated compounds have shown antioxidant, antibacterial, antifungal, antiviral, antiparasitic, anthelmintic, anti-inflammatory, anticoagulant, anti-aging, cytotoxic, antitumoral, and antiproliferative properties. In vivo studies have demonstrated hepatoprotective, skincare, and cardiac-glycoside-like effects. While crude extracts and bufadienolide-rich fractions have shown toxic effects in 2-week-old chicks, guinea pigs, and Artemia salina, no toxicity has been reported in goats, broiler chickens, laying hens, or human erythrocytes. Although K. daigremontiana-based products are commercially available as dietary supplements with various health claims, these lack scientific validation. Despite the potential pharmaceutical applications of K. daigremontiana, further research is needed to determine its effects, dosage, mechanisms, long-term safety, and side effects, with clinical studies essential to validate its therapeutic potential.

Scientia Pharmaceutica doi: 10.3390/scipharm94020026

Authors: Orlando Maia Barboza Luan Henrique Santos Barreto Felipe dos Santos Mendes Ivana Ferreira Simões Luís Filipe Gomes Santos Carlos Fernando da Silva Ferreira Luís Guilherme dos Santos de Sant’Anna Tainá Santos Lima Kaique Souza Santos de Jesus Saul Vislei Simões da Silva Victor Pena Ribeiro Silvia Lima Costa Gustavo Souza dos Santos Lourdes Cardoso de Souza Neta Aníbal de Freitas Santos Júnior

Quercetin, one of the most abundant flavonoids in nature, has attracted the attention of many researchers due to its chemical and biological properties. A series of metal–quercetin complexes (Cu2+, Co2+, Zn2+, Sn2+, Al3+, Cd2+ and Mg2+) were synthesized and systematically characterized by Fourier transform infrared spectroscopy (FTIR), UV-visible spectroscopy (UV–Vis) and nuclear magnetic resonance (NMR). These analyses confirmed that the complexes predominantly form through coordination with the 4-carbonyl group and adjacent phenolic hydroxyls. This induces measurable shifts in the ν(C=O), ν(O–H), and π→π* transition bands relative to free quercetin. The antioxidant capacity of the complexes was evaluated using 2,2-Diphenyl-1-Picrylhydrazyl (DPPH•) radical scavenging method, 2,2′-Azinobis(3-Ethylbenzothiazoline-6-Sulfonic Acid) (ABTS•)+ radical activity, and Ferric Reducing Antioxidant Power (FRAP) assay. Several complexes exhibited higher radical scavenging efficiency than quercetin, with inhibition percentages exceeding 80% in the DPPH• and ABTS•+ assays. Others showed reduced activity due to the masking of redox-active hydroxyl groups during metal coordination. FRAP results corroborated these trends, indicating metal-dependent modulation of reducing power. Antimicrobial evaluation revealed that selected complexes were more active than free quercetin, particularly against Staphylococcus aureus and Candida spp., with minimum inhibitory concentrations (MICs) ranging from 75–250 μg mL−1. Overall, metal complexation significantly alters the electronic structure and biological behavior of quercetin, highlighting the potential of metal–flavonoid complexes as multifunctional antioxidants and antimicrobials.

Scientia Pharmaceutica doi: 10.3390/scipharm94010025

Authors: Valentina Paganini Mariacristina Di Gangi Patrizia Chetoni Silvia Tampucci Daniela Monti Susi Burgalassi

Daily exposure to blue light emitted by digital devices has raised concerns about oxidative stress-mediated damage to the ocular surface. Despite growing interest, validated in vitro models to study blue light-induced oxidative stress in corneal epithelial cells remain limited. A reproducible in vitro method was developed using rabbit corneal epithelial (RCE) cells exposed to blue LED light (405 nm). Irradiation parameters were optimized to induce oxidative stress without causing overt cytotoxicity. Cellular viability, intracellular ROS production, and mitochondrial oxidative stress were assessed. The model was validated using reference antioxidants (ascorbic acid and oleuropein), oleuropein formulated in a drug-in-cyclodextrin-in-liposome system (OLE-DCL), and two commercial ophthalmic formulations applied before or after irradiation. Blue light irradiation at 4.57 W/m2 for 30 min significantly increased intracellular and mitochondrial ROS levels while preserving cell viability, indicating sublethal photo-oxidative stress. Ascorbic acid effectively suppressed ROS generation, whereas free oleuropein showed reduced efficacy, likely due to photosensitivity. OLE-DCL significantly enhanced antioxidant activity under irradiation. The model also discriminated between protective and restorative treatment strategies. This study establishes a validated in vitro blue light-induced oxidative stress model for corneal epithelial cells, suitable for screening antioxidant compounds, formulations, and application strategies relevant to ocular surface protection.

Scientia Pharmaceutica doi: 10.3390/scipharm94010024

Authors: José Jailson Lima Bezerra Mateus Araújo da Luz Aline Peres Ferreira Joseilton Franco França Tatiana Porto Santos Anderson Angel Vieira Pinheiro Maria da Conceição de Menezes Torres

Globally, breast cancer is one of the most prevalent tumors in women and remains a major concern due to its high mortality rate. Although treatment options for this disease have evolved over the years, there are still many cases of recurrence and metastasis. In this context, considering the importance of evaluating less aggressive and more efficient therapeutic alternatives to aid in the treatment of breast cancer, the present study critically discusses the cytotoxic effects of diterpenoids isolated from Croton species (Euphorbiaceae). The articles were retrieved from different databases, from the first report published in 2005 to October 2025. A total of 115 diterpenoids were isolated from 15 Croton species and investigated against different breast cancer cell lines (MDA-MB-231, MCF-7, and MDA-MB-468). These compounds mainly belong to the kaurane group (40%), followed by clerodane (14%), tigliane (12%), and abietane (10%). Of this total, only 25 compounds showed promising results (IC50 = < 10 µM). The mechanisms of action of the compounds crokokaugenoid A, kongensin A, kongensin D, ent-16β,17α-dihydroxykaurane, and lauicyclone A have been reported. These compounds likely act by inducing apoptosis, autophagy, cell cycle arrest, inhibition of cell migration and invasion, and DNA fragmentation in breast cancer cell lines. To date, no randomized clinical trials have been conducted using Croton diterpenoids for the treatment of breast cancer. Therefore, further studies on the modulation of the immune response by these natural products are essential to better understand their immunotherapeutic activity in the tumor microenvironment during breast cancer progression.

Scientia Pharmaceutica doi: 10.3390/scipharm94010023

Authors: Katherine González-Berrio Miguel Ángel Puertas-Mejía

Brown algae are a valuable source of bioactive secondary metabolites, particularly polyphenols and sulfated polysaccharides with photoprotective and antioxidant activities. Among them, fucoidan stands out for its biocompatibility, biodegradability, and demonstrated photoprotective effects, mainly through antioxidant and anti-photoaging properties, making it a promising natural component for UV-protective formulations. This study developed polyelectrolyte complex sub-micron particles based on fucoidan and chitosan (F/Cs) to encapsulate quercetin (Q) as a natural UV-active antioxidant. Fucoidan from Sargassum filipendula was extracted and fractionated by ultrafiltration. An RCBD was used to optimize pH and F/Cs mass ratio. The optimal blank formulation (F/Cs = 1:1, pH 5.0) yielded sub-micron colloidal carriers with a mean hydrodynamic diameter of 421 ± 23 nm (PDI 0.252 ± 0.059) with ζ = +43.5 ± 1.6 mV. Quercetin-loaded particles (F/Cs/Q = 1:1:0.5) presented 915 ± 87 nm (PDI 0.278 ± 0.093) and ζ = +54.6 ± 1.2 mV. UV–Vis spectra evidenced UVB and partial UVA absorption for fucoidan and broad UVA/UVB coverage for quercetin, preserved upon encapsulation. Antioxidant activity was retained post-encapsulation (EC50, DPPH: 0.094 mg/mL; ABTS: 0.0749 mg/mL). These results demonstrate the potential of fucoidan–chitosan colloidal systems as multifunctional, biodegradable carriers for natural photoprotective agents, supporting their application in next-generation dermatological and cosmeceutical formulations.

Scientia Pharmaceutica doi: 10.3390/scipharm94010022

Authors: Yoana Sotirova

Jojoba oil is a well-established skin-beneficial liquid wax with high value in topical formulations. Bigels, as preferred semi-solid dosage forms, serve as versatile platforms by incorporating hydrogels and oleogels to leverage their advantages and address their limitations. In this study, jojoba oil bigels were developed using sorbitan monostearate (20%, w/w) as an oleogelator and different hydrophilic bases, 1% Carbomer 940, 6% methylcellulose, or 20% Poloxamer 407 gel, with all concentrations expressed relative to the corresponding phase. Nine bigels were obtained by varying hydrogel-to-oleogel ratios (90:10–70:30). They were evaluated in terms of their organoleptic, microstructural, and textural characteristics. Both the hydrogel matrix type and the phase proportion impacted the studied properties. Carbomer bigels displayed the highest spreadability, methylcellulose formulations showed the greatest adhesiveness, and poloxamer systems exhibited maximum firmness and cohesiveness, with a comparatively more homogeneous phase distribution. The increase in oleogel content enhanced firmness and cohesiveness while modulating spreadability and adhesiveness in a hydrogel-dependent manner. Moreover, all designed formulations remained physically stable after centrifugation, but only those containing 80% carbomer gel or 70% or 80% poloxamer gel preserved their mechanical characteristics without significant changes after freeze-thawing. Besides identifying three promising biphasic dermal drug delivery platforms, these findings reinforce the tunability of bigels through the careful component selection.

Scientia Pharmaceutica doi: 10.3390/scipharm94010021

Authors: Héctor Iván Saldívar-Cerón

Once-monthly injectable therapies targeting glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and adjacent metabolic pathways are moving from a conceptual goal to a plausible next step for type 2 diabetes (T2D) and obesity. The most clinically advanced program is maridebart cafraglutide (MariTide), a long-acting GLP-1 receptor agonist conjugated to an Fc-containing scaffold that also mediates sustained GIP receptor antagonism. Across phase 2 trials, once-monthly maridebart has produced clinically meaningful weight loss (~12–16% in adults without diabetes; ~8–12% in those with T2D), together with HbA1c reductions of ~1.2–1.6 percentage points, with a safety profile broadly consistent with GLP-1-based therapy. An exploratory every-8-weeks regimen showed attenuated efficacy, suggesting that monthly dosing may represent a practical lower boundary for maintaining therapeutic exposure and metabolic effect in this format. Beyond maridebart, a rapidly expanding pipeline—including ultra-long-acting GLP-1 analogs, dual GLP-1/GIP agonists, long-acting GIPR antagonists, amylin receptor agonists, and emerging thyroid hormone receptor beta (THRβ) agonists—is actively testing monthly regimens or induction-to-monthly maintenance strategies; however, most readouts remain early and are frequently limited to conference presentations or sponsor communications. Accordingly, much of the pipeline evidence should be interpreted as early-phase and non-peer-reviewed, and therefore hypothesis-generating. Key uncertainties include long-term durability, cardiometabolic outcomes, immunogenicity, and interindividual variability in response, which will ultimately determine how once-monthly regimens integrate with established weekly standards in routine care.

Scientia Pharmaceutica doi: 10.3390/scipharm94010020

Authors: Sophia S. Borisevich Edward M. Khamitov Gulshat A. Masyagutova Olga I. Yarovaya Sergey L. Khursan

A comprehensive MD + QC methodology was developed and applied to evaluate various aspects of Arbidol interactions with functional amino acids of surface proteins of influenza virus and SARS-CoV-2. The spatial structure, solvation features, conformational behavior of Arb AA (AA–Trp, Tyr, Phe, and Val) complexes were established, and the statistics of intermolecular interactions in the complex were described. It was found that Arb can participate in strong and long-lived π-π stacking interactions with aromatic amino acids. The binding energy (BE) of Arbidol and amino acids in aqueous solution was estimated using an explicit solvation model, QTAIM analysis and correlation of BE vs. total electron density at the bond critical points of the complex. Theoretical calculations were validated by experimental studies of fluorescence (FL) quenching of aromatic AA by Arbidol. Spectral-fluorescent properties of Arbidol hydrochloride in aqueous solutions were studied, and the luminescence quantum yield for the electronically excited state of Arb was determined.

Scientia Pharmaceutica doi: 10.3390/scipharm94010019

Authors: Christophor Lazov Krassimira Yoncheva Marta Slavkova

Lipid nanoparticles have been a subject of intense scientific interest in recent years due to their inherent biocompatibility, versatile delivery routes, drug loading and potential large-scale production. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are matrix lipid nanoparticles that differ in their lipid composition and, specifically, the presence of liquid lipid in the latter. Their production is straightforward and relatively inexpensive. They provide an additional specific advantage for dermal delivery in the treatment of atopic dermatitis, as they can carry various drugs and even ameliorate the skin condition on their own. The chronic character and the observed predominance of atopic dermatitis in the pediatric population further justify the utility of improved therapeutic strategies and the application of SLNs and NLCs specifically. Therefore, in the current review, we aimed to systematically collect the available literature on this topic and to evaluate where we stand in terms of scientific and practical knowledge. The observations show significant potential for clinical translation for both SLNs and NLCs in the near future. However, some key limitations were identified and discussed. The novelty of this review lies in its systematic consolidation and critical discussion of SLNs and NLCs specifically in the context of atopic dermatitis.

Scientia Pharmaceutica doi: 10.3390/scipharm94010018

Authors: Jorge L. Gutierrez-Pajares Isabel Gómez-Betancur Francisco León

Cobalamin, also known as vitamin B12, is an essential cofactor involved in one-carbon metabolism, mitochondrial function, and epigenetic regulation. As humans rely entirely on dietary intake of cobalamin paired with a highly coordinated absorption and transportation system, disruptions to this metabolic process can have profound health consequences. Breast cancer, the most frequently diagnosed malignancy among women worldwide, exhibits distinct metabolic adaptations, including altered cobalamin uptake and dependency on B12-driven biochemical pathways. This review summarizes the molecular mechanisms governing cobalamin metabolism, with a focus on absorption, transport, and intracellular processes relevant to breast cancer biology. We then examine how breast cancer cells reprogram these pathways. Finally, we evaluate emerging pharmaceutical strategies that target cobalamin metabolism, including B12-based imaging probes, cobalamin-conjugated drug delivery systems, and inhibitors of B12-dependent enzymes. Although these approaches show promise, further research is needed to define subtype-specific metabolic signatures, optimize cobalamin-mediated drug targeting, and clarify how systemic B12 status influences therapeutic response. By integrating biochemical, epidemiological, and translational perspectives, this review outlines how cobalamin-centered strategies may contribute to more precise diagnostic and therapeutic options for breast cancer.

Scientia Pharmaceutica doi: 10.3390/scipharm94010017

Authors: Ana María Sepúlveda Marcela Manrique-Moreno Sofía Echeverri-Gaviria Gloria A. Santa-González

Triple-negative breast cancer is the subtype with the worst prognosis and has limited treatment options. Bioactive peptides are a promising alternative, having demonstrated antitumor properties with a mechanism of action involving the cell membrane. In this study, we evaluated the Ctn-2 peptide, a fragment of crotalicidin (Ctn), which has shown antitumor activity with highly lytic characteristics but is not selective in non-tumor cells. We evaluated the antitumor activity of the peptide Ctn-2 in triple-negative breast cancer cells and its selectivity over non-tumoral cells. Comparative analyses with LTX-315 and biophysical studies on model membranes indicate that Ctn-2 preferentially interacts with cancer-associated lipids. Functional assays further show that its action involves controlled membrane disruption and associated cellular responses. We also examined the combined effect of Ctn-2 and doxorubicin, finding that Ctn-2 selectively enhanced cytotoxicity in tumor cells and potentiated the activity of conventional chemotherapy. Overall, the results indicate that Ctn-2 is a membrane-active peptide with selective antitumor potential and the ability to improve chemotherapeutic efficacy.

Scientia Pharmaceutica doi: 10.3390/scipharm94010016

Authors: Malika Mekhalfi Sabine Berteina-Raboin

Mucuna pruriens (M. pruriens) is a legume that attracts researchers for its benefits and has been used for centuries in Ayurvedic medicine. While its effectiveness has long been recognized, in-depth studies have shown that its activity is mainly due to its high levodopa (L-Dopa) content, but not exclusively. It also contains other structures that can improve its effectiveness and reduce the side effects encountered when using synthetic L-Dopa. Similarly, other molecules that selectively inhibit certain enzymes are present. Various methods of varying effectiveness have been used to extract the active ingredients, and recently, progress has been made in extraction methods. Clinical studies already exist demonstrating its therapeutic benefits, similar to those of synthetic L-Dopa, for several conditions, and showing the limitations of certain side effects such as dyskinesias. Further studies and clinical trials are still needed, but this plant could be a very good alternative in countries that do not have or no longer have access to certain drugs. This legume can be grown without difficulty in these countries, as it has the advantage of being resistant to drastic climatic conditions.

Scientia Pharmaceutica doi: 10.3390/scipharm94010015

Authors: Antoniy A. Kladiev Elena V. Uspenskaya Mikhail G. Baryshev Vasilii A. Ivlev Vasilii G. Vasil’ev Samvel S. Barsegyan Ainaz Safdari

The clinical efficacy of chemotherapy against rapidly proliferating cells stimulates both the development of new agents and the reassessment of established drugs. Spectroscopic methods (UV, FT-IR, and 1H NMR) were applied to characterize prospidium chloride and related substances. The FT-IR spectrum of prospidium chloride, arising from vibrational transitions within the alkyl fragments of the dispirotripiperazinium cation, is reported with band assignments. Electronic transitions between molecular orbitals are analyzed using quantum–mechanical selection rules (Laporte and spin selection rules). The n→σ* transition (ΔS = 0) corresponds to the absorption maximum at λmax = 282 ± 0.40 nm (ε = 3.89 ± 0.08 L·mol−1·cm−1). A 1H NMR spectrum (700 MHz) was used to assign chemical shifts δ (ppm), J-coupling constants (Hz), and gauche conformational features of prospidium chloride and its dihydroxy and epoxy impurities. Quantitative 1H NMR (qNMR) was applied to determine the content of the active pharmaceutical ingredient and related substances. The methods provide complementary structural information for the characterization of prospidium chloride.

Scientia Pharmaceutica doi: 10.3390/scipharm94010014

Authors: Nerlis Pájaro-Castro Paulina Valenzuela-Hormazábal Erick Díaz-Morales Kenia Hoyos Karina Caballero-Gallardo David Ramírez

Pseudomonas aeruginosa is a Gram-negative pathogen with a remarkable capacity to acquire multiple resistance mechanisms, severely limiting current therapeutic options. Consequently, the identification of new antimicrobial agents remains a critical priority. In this study, an integrated in silico-guided strategy was applied to identify small molecules with antibacterial potential against P. aeruginosa, targeting the quorum-sensing regulator LasR (PDB ID: 2UV0) and elastase (PDB ID: 1U4G). Pharmacophore modeling was performed for both targets, followed by ligand-based virtual screening, structure-based virtual screening (SBVS), and MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) binding free energy calculations. Top-ranked compounds based on predicted binding affinity were selected for in vitro cytotoxicity and antibacterial evaluation. Antimicrobial activity was assessed against three P. aeruginosa strains: an American Type Culture Collection (ATCC) reference strain, a clinically susceptible isolate, and an extensively drug-resistant (XDR) clinical isolate. SBVS yielded docking scores ranging from −6.96 to −12.256 kcal/mol, with MM-GBSA binding free energies between −18.554 and −88.00 kcal/mol. Minimum inhibitory concentration (MIC) assays revealed that MolPort-001-974-907, MolPort-002-099-073, MolPort-008-336-135, and MolPort-008-339-179 exhibited MIC values of 62.5 µg/mL against the ATCC strain, indicating weak-to-moderate antibacterial activity consistent with early-stage hit compounds. MolPort-008-336-135 showed the most favorable activity against the clinically susceptible isolate, with an MIC of 62.5 µg/mL, while maintaining HepG2 cell viability above 70% at this concentration and an half-maximal inhibitory concentration (IC50) greater than 500 µg/mL. In contrast, all tested compounds displayed MIC values above 62.5 µg/mL against the XDR isolate, reflecting limited efficacy against highly resistant strains. Overall, these results demonstrate the utility of in silico-driven approaches for the identification of antibacterial hit compounds targeting LasR and elastase, while highlighting the need for structure–activity relationship optimization to improve potency, selectivity, and activity against multidrug-resistant P. aeruginosa.

Scientia Pharmaceutica doi: 10.3390/scipharm94010013

Authors: Karina Kleinfelder Paola Lecca Roberta Valeria Latorre Chiara Mortali Sara Casati Sofia Vanerio Claudio Sorio Paola Melotti

Pharmacological modulators of CFTR have significantly changed the cystic fibrosis (CF) phenotype of subjects affected by this multi-organ disease. Here, we evaluated the CFTR function analysis (short-circuit chamber in colonoids) in response to Elexacaftor/Tezacaftor/Ivacaftor (ETI) with the clinical benefits of in vivo treatment with ETI in ten CF subjects. We found that the functional response of ETI-corrected PDROS significantly correlated with the absolute change in the sweat chloride test. Thus, our work reinforces the use of organoid-derived human intestinal monolayers to guide clinicians in selecting CFTR-targeted therapies.

Scientia Pharmaceutica doi: 10.3390/scipharm94010012

Authors: Seon-Hyeok Kim Se Jeong Kim Eun Ji Ko Hae Ran Lee Seong Min Hong Se Hwan Ryu Dae Hee Lee Young Guk Kim Jeong Yun Yu Jae Kang Lee Mi Kyeong Lee Sun Yeou Kim

Alzheimer’s disease and related neurodegenerative disorders are associated with progressive cognitive decline, primarily driven by cholinergic dysfunction and impaired synaptic signaling. Hericium erinaceus, also known as lion’s mane mushroom, has been reported to promote neuronal differentiation and synaptic plasticity. In this study, a standardized H. erinaceus extract powder (HEP) was prepared from fruiting bodies and quantified using hericene A as a marker compound. The neuroprotective effects of HEP were then evaluated in both cellular and animal models of scopolamine-induced cognitive dysfunction. Pretreatment of SH-SY5Y human neuroblastoma cells with HEP (5–25 μg/mL) significantly improved cell viability and reduced scopolamine-induced apoptosis, while enhancing the activation of neuroplasticity-related signaling proteins, including brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and extracellular signal-regulated kinase (ERK). In vivo, oral administration of HEP (300 mg/kg) to scopolamine-treated ICR mice markedly improved cognitive performance, increasing the recognition index to 63.8% compared with 41.6% in the scopolamine group, and enhancing spontaneous alternation in the Y-maze test to 59.6%. These cognitive improvements were accompanied by preserved hippocampal neuronal structure and increased BDNF immunoreactivity. Additionally, HEP improved cholinergic function by restoring serum acetylcholine levels and reducing acetylcholinesterase activity. Collectively, these findings suggest that standardized HEP exerts neuroprotective and cognition-enhancing effects via modulation of cholinergic markers and activation of BDNF-mediated neuroplasticity, highlighting its potential as a functional food ingredient or nutraceutical for preventing cognitive decline related to cholinergic dysfunction.

Scientia Pharmaceutica doi: 10.3390/scipharm94010011

Authors: Sreenivas Avula Satish Koppireddi Micky D. Tortorella Cleopatra Neagoie

This study reports the exclusive and rapid synthesis of twenty-four derivatives of 1-((mono/bis)trifluoromethyl)phenyl-3-(4-arylthiazol-2-yl)thioureas (series 7, 9 and 11), along with their antimicrobial activities against Candida albicans, Mycobacterium smegmatis and seven additional bacterial strains. The anticancer potential of these compounds was evaluated against various human cancer cell lines, including A549 (lung adenocarcinoma), HeLa (cervical carcinoma), IMR32 (neuroblastoma), MCF-7 (breast adenocarcinoma), HCT116 (colon cancer) and DU145 (prostate cancer). Among these, 1-(3,5-bistrifluoromethylphenyl)-3-(thiazol-2-yl)thiourea (7i) and 1-(4-trifluoromethylphenyl)-3-(4-(3-chlorophenyl)thiazol-2-yl)thiourea (11h) demonstrated significant antimicrobial activity against M. luteus, S. aureus, S. aureus 1 and C. albicans. Additionally, 1-(4-(3-chlorophenyl)thiazol-2-yl)-3-(3-trifluoromethylphenyl)thiourea (9g) and 1-(4-trifluoromethylphenyl)-3-(4-(2-fluorophenyl)thiazol-2-yl)thiourea (11g) showed activity against Mycobacterium smegmatis. The bioassay tests indicated that many of the thiourea derivatives exhibited moderate activity against the A549, HeLa, MCF-7 and HCT116 cancer cell lines.

Scientia Pharmaceutica doi: 10.3390/scipharm94010010

Authors: Tibor Rák Edit Ormai Györgyi Horváth

Mental health disorders, particularly anxiety and insomnia, are increasingly prevalent worldwide, prompting interest in herbal-based complementary therapies. This study surveyed 168 Hungarian healthcare professionals to evaluate their knowledge and recommendations regarding herbal sedatives and analyzed seven commonly suggested OTC products available in Hungary, using thin-layer chromatography (TLC) and UV–Vis spectrophotometry according to the European Pharmacopoeia. The survey revealed that 86.9% of respondents recommend herbal products for nervous system complaints, with Valeriana officinalis and Melissa officinalis being the preferred ingredients. Herbal teas and traditional herbal medicines were the most frequently suggested product categories. Laboratory analysis confirmed the presence of marker compounds in all tested products; however, significant variability in active ingredient concentrations was observed. One homeopathic product contained an unidentified alkaloid-like compound, raising safety concerns. Essential oil yields from tea mixtures also varied markedly, and some products did not meet pharmacopoeial standards for hypericin content. These findings highlight the popularity of phytotherapy among healthcare professionals and the need for stricter quality control of OTC herbal sedatives. Future research should include multi-batch analyses and clinical trials to establish robust evidence for efficacy and safety.

Scientia Pharmaceutica doi: 10.3390/scipharm94010009

Authors: Jesus Magdiel García-Díaz Asbiel Felipe Garibaldi-Ríos Martha Patricia Gallegos-Arreola Filiberto Gutiérrez-Gutiérrez Jorge Iván Delgado-Saucedo Moisés Martínez-Velázquez Ana María Puebla-Pérez

Drug discovery is a complex and expensive process in which only a small proportion of candidate molecules reach clinical approval. Computational methods, particularly computer-aided drug design (CADD), have become fundamental to accelerate and optimize early stages of discovery by integrating chemical, biological, and pharmacokinetic information into predictive models. This review outlines a complete computational workflow for chemical compound analysis, covering molecular structure generation, database selection, evaluation of absorption, distribution, metabolism, excretion and toxicity (ADMET), target prediction, and molecular docking. It focuses on freely accessible and web-based tools that enable reproducible, cost-effective, and scalable in silico studies. Key platforms such as PubChem, ChEMBL, RDKit, SwissADME, TargetNet, and SwissDock are highlighted as examples of how different resources can be integrated to support rational compound design and prioritization. The article also discusses essential methodological principles, data curation strategies, and common limitations in virtual screening and docking analyses. Finally, it explores future directions in computational drug discovery, including the incorporation of artificial intelligence, multi-omics integration, and quantum simulations, to enhance predictive accuracy and translational relevance.

Scientia Pharmaceutica doi: 10.3390/scipharm94010008

Authors: Aida Lahmar Balkis Abdelaziz Nahla Gouader Abir Salek Imen Waer Leila Chekir Ghedira

Ultraviolet B radiation is a major cause of skin aging, cellular senescence, and inflammaging, mediated by the excessive production of reactive oxygen species (ROS) and induction of apoptosis. This study evaluated the photo-protective effects of astaxanthin, one of the strongest natural antioxidants, in UVB-treated keratinocytes. The antioxidant capacity of astaxanthin was evaluated using ABTS, DPPH, and NBT/riboflavin/SOD assays. HaCaT cells were exposed to 30 mJ/cm2 of UVB radiation. Photoprotective effects and accumulated ROS were evaluated in UVB-irradiated HaCaT cells by MTT and DCFH-DA assays. Nitric oxide levels were quantified using the Griess reagent. Apoptosis was assessed by dual staining using acridine orange/ethidium bromide, lysosomal integrity by acridine orange uptake, and cell migration by scratch assay. Cell adhesion was assessed on ECM-coated Nunc plates. Finally, we formulated a 0.5% astaxanthin-enriched cream. Astaxanthin mitigated UVB-induced damage by reducing intracellular ROS levels by 3.7-fold, decreasing nitric oxide production to 29.8 ± 7.7% at the highest concentration, and maintaining lysosomal integrity. The carotenoid significantly enhanced cell viability, increasing it from 60.64 ± 8.3% in UV-treated cells to 102.1 ± 3.22% at 40 µM. Moreover, treated cells showed a significant reduction (p < 0.001) in the apoptotic rate (37.7 ± 3.1 vs. 87.7 ± 3.8 in UVB-irradiated cells, as evidenced by reduced chromatin condensation and nuclear fragmentation. Astaxanthin also enhanced tissue repair, as evidenced by increased cell migration and adhesion to several extracellular matrix (ECM) proteins (poly-L-lysine, laminin, fibrinogen, vitronectin and collagen I). In silico molecular docking predicted strong binding affinities between astaxanthin and key cellular targets, including JAK2 (−9.9 kcal/mol, highest affinity), STAT3, FAK, COX-2, NF-k-B, MMP2, and MMP9. The formulated cream demonstrated an in vitro SPF of 7.2 ± 2.5. Astaxanthin acts as a multifunctional photoprotective compound, providing a strong rationale for its incorporation into cosmetic and dermatological formulations, as further supported by the successful formulation and in vitro SPF estimation of an astaxanthin-enriched cream.

Scientia Pharmaceutica doi: 10.3390/scipharm94010007

Authors: Mateo Pérez-R G. Orozco A. González-Ruiz Miriam V. Flores-Merino

The synthesis of sodium carboxymethylcellulose (NaCMC) from lignocellulosic pineapple stubble provides a renewable alternative to conventional cellulose sources for pharmaceutical applications. This study aimed to obtain NaCMC from pineapple biomass, characterize it according to pharmacopoeial specifications, and formulate hydrogels as a physicochemical proof-of-concept for future drug delivery and tissue regeneration applications. NaCMC was successfully synthesized and met the requirements of the Mexican Pharmacopoeia. Hydrogels were prepared by blending NaCMC with gelatin and crosslinking with citric acid. Spectroscopic, morphological, and thermal analyses confirmed the structural equivalence between pineapple-derived NaCMC (NaCMC-Pi) and commercial NaCMC (NaCMC-Co). Swelling and gel fraction studies showed that NaCMC-Pi hydrogels exhibited a higher gel fraction, indicating a more crosslinked network, which corresponded to lower swelling capacity but higher thermal stability compared to NaCMC-Co hydrogels. Overall, these results demonstrate that pineapple stubble is a viable source of pharmaceutical-grade NaCMC and that the resulting hydrogels provide a robust physicochemical basis for future biomedical validation. The use of agro-industrial residues additionally offers a complementary sustainability benefit without compromising pharmaceutical performance.

Scientia Pharmaceutica doi: 10.3390/scipharm94010006

Authors: Pratikshya Paudel Prabir Kumar Gharai

Neurodegeneration—driven by oxidative stress, chronic inflammation, and protein aggregation—underlies disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and stroke. Current pharmacological treatments are largely symptomatic and do not restore lost neural circuitry, motivating regenerative approaches. Mesenchymal stem cells (MSCs) provide neurotrophic and immunomodulatory benefits and can support synaptic repair, yet robust conversion into mature, electrophysiologically functional neurons remain challenging and often depends on complex inducer cocktails with translational limitations. Crocin, a saffron-derived carotenoid, is reported to enhance neurogenesis and neuroprotection in preclinical models through pathways including Wnt/β-catenin, Notch1, CREB/BDNF, and modulation of GSK-3β, while reducing apoptosis and inflammatory signaling. Here, we synthesize evidence supporting crocin’s neuroprotective and proneurogenic activity and propose a testable hypothesis that crocin-based or crocin-modified formulations could be evaluated as adjuncts to guide MSC neuronal lineage commitment. Importantly, direct evidence that crocin alone can drive MSC trans-differentiation into fully functional neurons is currently insufficient; future work should define functional benchmarks (electrophysiology, synaptogenesis, and phenotypic stability) and rigorously validate safety, dosing, and delivery strategies for neuroregenerative translation.

Scientia Pharmaceutica doi: 10.3390/scipharm94010005

Authors: Oleksandra Havrylenko Yuliya Kondratova Kateryna Typlynska Liliya Logoyda

The main goal of this study was to develop methods for quality control of naftifine hydrochloride in solution and cream forms, focusing on “Quantitative Determination” and “Related Impurities.” New, precise, accurate, and environmentally friendly high performance liquid chromatography (HPLC) methods were developed for the determination of naftifine hydrochloride and its impurities. “Quantitative determination” was performed using a diode array detector at 254 nm with an isocratic mobile phase (1.154 g of ammonium acetate R dissolved in 300 mL of water R, followed by the addition of 0.2 mL of glacial acetic acid R, mixed well) and methanol (30:70). The chromatographic columns Gemini C18 and Luna C18 were used. “Related impurities” were separated at 270 nm using a gradient mobile phase consisting of 10 M sodium octanesulfonate, 0.4 g/L disodium hydrogen phosphate anhydrous solution (pH 6.5), acetonitrile, and the Synergi Hydro-RP chromatographic column. The developed method, validated according to ICH guidelines, showed run times of 55 min for impurity analysis and 6 min for active ingredient determination. The methods were successfully applied to the quality control of the solution and cream.

Scientia Pharmaceutica doi: 10.3390/scipharm94010004

Authors: Edwin Y. Valladares Chávez Luis A. Moreno-Rocha Lucia Ortega Cabello Ponciano García-Gutiérrez Jorge E. Miranda-Calderón

The accurate determination and quantification of praziquantel are essential for optimizing its therapeutic effectiveness in treating schistosomiasis and neurocysticercosis, two significantly neglected tropical diseases. Its challenging physicochemical profile, extensive metabolism, and stereochemical complexity requires robust analytical methods for reliable quantification in clinical, veterinary, and pharmaceutical samples. This review provides a comprehensive and critical evaluation of analytical strategies used for PZQ determination, spanning fluorometric and radiometric assays, HPLC–UV, LC–MS, LC–MS/MS, and enantioselective chromatographic approaches. Particular emphasis is placed on the evolution toward highly sensitive LC–MS/MS methods and their alignment with contemporary regulatory expectations, including ICH M10 requirements. These advancements have significantly improved sensitivity, specificity, and reproducibility, which are crucial for pharmacokinetic, pharmacodynamic, and bioequivalence studies. Enantioselective methods for distinguishing PZQ enantiomers and metabolites are discussed. The aim of these innovations is to increase praziquantel bioavailability, improve patient adherence, and support its continued use in mass drug administration programs. Finally, the review highlights implementation challenges in resource-limited settings and proposes analytical models to expand global bioanalytical capacity. Together, these insights provide a structured foundation for selecting and developing high-quality, regulatory-compliant analytical methods for PZQ.

Scientia Pharmaceutica doi: 10.3390/scipharm94010003

Authors: Eneida Azaret Montaño-Grijalva Francisco Rodríguez-Félix José Agustín Tapia-Hernández Enrique Márquez-Ríos Carmen Lizette Del-Toro-Sánchez Dora Evelia Rodríguez-Félix Ricardo Nalda-Molina Elizabeth Carvajal-Millan Carlos Gregorio Barreras-Urbina Itzel Yanira López-Peña Cielo Estefanía Figueroa-Enríquez

Currently, there are various approaches to the treatment of diabetes. Regarding type 2 diabetes (T2D), treatment focuses on blood glucose control. When changes in lifestyle do not achieve this glycemic control, the option is to start therapy with antidiabetic drugs such as metformin. However, long-term metformin use causes disturbances that may affect treatment approaches. This review examines recent advances in nanotechnology that have developed new forms of drug administration that can improve the efficacy of the treatment, where nanomaterials, nanostructures, and nanoparticle design are involved, so that they provide controlled and gradual release. The use of biopolymers (as drug delivery systems) has ensured biocompatibility, biodegradability, and low toxicity. There are several methods for obtaining a drug delivery system, including electrospinning, electrospraying, nanoprecipitation, etc. These systems improve drug delivery and can be used orally, transdermally, or intravenously, among means of administration. This review describes the new forms of the administration of metformin in the treatment of T2D, based on the encapsulation of metformin in polymeric matrices such as proteins, polysaccharides, and lipids, among others.

Scientia Pharmaceutica doi: 10.3390/scipharm94010002

Authors: Gleb Vladimirovich Petrov Aleksandr Andreevich Nazarov Alena Mikhailovna Koldina Anton Vladimirovich Syroeshkin

Hyaluronidase and its modified analogs are clinically significant enzyme-based pharmaceuticals used to treat fibrosis, increase tissue permeability, and improve drug diffusion. While pharmacopeial quality control methods are well defined, scientific literature provides limited information about the physicochemical evaluation of such enzyme pharmaceuticals, necessitating a more holistic analytical approach. Commercial pharmaceuticals of hyaluronidase and its modified analog were analyzed using a combination of dynamic light scattering, infrared spectroscopy, and detection of intrinsic radiothermal emission (RTE). Dimensional characteristics were studied using a Zetasizer Nano ZSP (ZetasizerNano ZSP, Malvern Instruments, Malvern, UK) confirmed theoretical diameters of 5–8 nm, consistent with experimental values (6–8 nm). Fourier-Transform infrared spectroscopy (FTIR) (Agilent Cary 630, Agilent Technologies, Santa Clara, CA, USA) revealed characteristic transmission bands for the modified enzyme at 1464, 1448, 1326, 1158, and 1010 cm−1, confirming structural modification. RTE measurements using a TES-92 detector (TES Electrical Electronic Corp., Taipei, Taiwan) demonstrated a correlation between emission intensity and shelf life: 12.8 ± 0.8 µW/m2 for proper shelf-life samples, 8.3 ± 0.8 µW/m2 for six-month-expired, and 5.1 ± 1.0 µW/m2 for one-year-expired pharmaceuticals. The study offers a promising supplementary tool for pharmaceutical quality control of hyaluronidase-based drugs.

Scientia Pharmaceutica doi: 10.3390/scipharm94010001

Authors: Deepak Kulkarni Sanjay Pekamwar

Rosuvastatin calcium is a promising lipid-lowering agent and the drug of choice in hyperlipidemia. Conventional solid oral delivery of rosuvastatin is limited by its poor solubility and ultimately poor bioavailability. An attempt was made to fabricate the cocrystals of RSC for enhancing solubility and bioavailability. Cocrystals were prepared by a microwave synthesiser-assisted solvent evaporation technique with multiple cocrystal formers. Rosuvastatin-Ascorbic acid (RSC-AA) cocrystals showed the highest solubility (~5-fold increased) amongst all twenty drug-coformer combination (DCC). RSC-AA cocrystals (1:1 ratio) were further characterized by various analytical techniques like FTIR, DSC and XRD to confirm the formation of cocrystals. RSC-AA cocrystals also showed improved flow properties and compressibility in comparison with pure drug, and it was demonstrated using the SeDeM diagram. RSC-AA cocrystals were further formulated into an immediate-release tablet by implementing experimental optimization. Comparative dissolution study of the cocrystal and pure drug tablet revealed improved dissolution after cocrystallization. RSC-AA cocrystal tablet showed the % drug release of 95.61 ± 3.94 while RSC pure drug showed the drug release of 67.83 ± 3.29. In vivo pharmacokinetic analysis showed significant improvement in systemic availability and cumulative absorption of the drug. The peak plasma concentration (Cmax) for RSC pure drug was 13.924 ± 0.477 μg/mL, while RSC-AA cocrystals showed a peak plasma concentration of 22.464 ± 0.484 μg/mL. Area Under Curve (AUC) of RSC-AA cocrystal was also significantly greater compared to the pure drug. In the stability study analysis, the shelf life was calculated from a graphical method and was found to be around 34.58 months for RSC-AA cocrystal tablets and 19.87 months for RSC pure drug tablets, which indicates improved stability with cocrystallization. Overall, the cocrystallization resulted in significant improvement in dissolution and solubility of RSC.

Scientia Pharmaceutica doi: 10.3390/scipharm93040062

Authors: Kar Lee Heesoo Kim Jong Song Olena Sydorchuk Wong Ka Fai Isabella Rosellini Hongseok Kim Kian Lau Michael Gold Kyuho Yi

Injectable biostimulatory agents such as poly-L-lactic acid (PLLA), polycaprolactone (PCL), and calcium hydroxyapatite (CaHA) have emerged as key tools in regenerative aesthetics due to their ability to stimulate adipogenesis and adipocyte metabolic activity, enhance collagen production, and improve dermal quality. This review aimed to provide an updated synthesis of the role of these agents in adipocyte stimulation, focusing on their mechanisms of action, clinical efficacy, and therapeutic applications. A comprehensive search of the MEDLINE, PubMed, and Ovid databases was conducted for studies published from 2018 onward, including in vitro and in vivo experiments, randomized controlled trials, and observational studies, which were evaluated according to the Oxford Centre for Evidence-Based Medicine hierarchy. The findings demonstrated that PCL promotes adipose-derived stem cell differentiation and extracellular matrix remodeling, while PLLA exhibits dual effects on collagen synthesis and adipocyte stimulation, with clinical trials such as the SPLASH study confirming significant improvements in dermal thickness and adipogenesis. CaHA provided immediate volumizing benefits with long-term tissue regeneration, and innovative approaches including combination therapies and novel injection protocols expanded clinical applications. Overall, PLLA, PCL, and CaHA represent effective and versatile biostimulatory agents that support natural and durable outcomes in aesthetic practice. Nevertheless, the absence of large-scale trials and standardized protocols highlights the need for further research to optimize safety, efficacy, and long-term treatment strategies.

Scientia Pharmaceutica doi: 10.3390/scipharm93040061

Authors: Nithin Vidiyala Pavani Sunkishala Preethi Mandati Prashanth Parupathi Dinesh Nyavanandi

Over the last decade, additive manufacturing (AM) has been widely investigated for developing on-demand, patient-centric, and personalized medications. Among various AM techniques, fused deposition modeling (FDM), semi-solid extrusion (SSE), inkjet printing, binder jet printing, stereolithography (SLA), and selective laser sintering (SLS) have been most widely studied for developing simple and complex pharmaceutical medications. Implementing the AM platform enables decentralized manufacturing of medications at the hospitals and clinical sites. The dose and release profiles of the dosage forms can be tailored based on patient needs, providing flexibility to the physician. In fact, streamlining the AM process into a continuous manufacturing process equipped with process analytical technology (PAT) tools will ensure the manufacturing and delivery of safe and efficacious medications to the patient population. Complex medications, such as polypills, which are complex and time-consuming to manufacture using traditional manufacturing techniques, can be printed quickly using the AM approach. The pediatric patient population can be attracted to medication by printing the dosage forms with a geometry of interest. The AM platform can be integrated with artificial intelligence (AI) and health records to accelerate drug development and tailor medications based on patient conditions. Despite the various advantages that the AM platform brings to the pharmaceutical field, a few limitations, such as scalability, material innovation, secondary processing, and regulatory evolution, need to be addressed. This review article compares the advantages and limitations of the existing AM techniques along with a note on the recent advancements and future perspectives.

Scientia Pharmaceutica doi: 10.3390/scipharm93040060

Authors: Zsuzsanna Takáts Attila Almási Judit Szalai-Szolcsányi Tünde Ambrus Nóra Papp

In this study, a terminological and grammatical survey of essential and fatty oils of plant origin was performed in the selected Austrian, Hungarian, Spanish, and Belgian pharmacopoeias from the 18th to 19th centuries. The Latin-language prescriptions were analysed for their content, sections, and indications, and then translated from Latin into English, and supplemented with the source plants. Oil types were categorised based on their preparation and origin. Most oils belong to essential oils in Ph. Austriaca I–IV, Ph. Belgica, and Ph. Hungarica I (20 in each). Cooked oils are described as having the highest number in Ph. Hispanica (21), while pressed oils are also included in a high ratio in Ph. Hisp. (18) and Ph. Austriaca V (15). At the same time, those from minerals are described only in Ph. Belg. (2) and Ph. Hisp. (5). Latin terms are used in preparation methods, including the most concise descriptions in Ph. Austriaca V and Ph. Hg. I. This comprehensive study provides new linguistic data on the oils of herbs in the selected pharmacopoeias. Studies of essential oils have recently been progressing, and this analysis might help in understanding information from old pharmacopoeias.

Scientia Pharmaceutica doi: 10.3390/scipharm93040059

Authors: Miroslav Radenković

Biopharmaceuticals are medical drugs produced by means of biotechnology. In contrast with small-molecule (traditional) drugs, which are usually synthesized chemically, biopharmaceuticals are derived from biological sources, including tissues, cells, or microorganisms. Biopharmaceuticals comprise a wide extent of therapies, such as vaccines, monoclonal antibodies, cell therapies, recombinant proteins, and gene therapies, as well as biosimilars. These products are designed to become important treatment options for different diseases, including cancer, autoimmune pathological disorders, andinfectious diseases. The development of biopharmaceuticals often includes multifaceted processes, involving genetic engineering and cellular culture techniques, to guarantee efficacy and safety. Accordingly, biopharmaceuticals’ legislation is a key component for ensuring the highest quality of medical products, as well as protecting public health. As a rapidly developing area inside the pharmaceutical industry, biopharmaceuticals represent a significant advancing stage in modern medicine, offering targeted therapies that can improve patient outcomes. Accordingly, this paper seeks to provide current state-of-the-art didactic information, including better insight into various challenges related to biopharmaceuticals’ development, classification, medical use, legislation and ethics.

Scientia Pharmaceutica doi: 10.3390/scipharm93040058

Authors: Divya Wali Shivakumar H. Nanjappa Avichal Kumar Rushikesh Shinde

Docetaxel (DTX)-loaded polymeric nanoparticles composed of Eudragit RL and RS 100 were developed by solvent evaporation using D-α-tocopheryl polyethene glycol 1000 succinate as an emulsifier and optimised by Central Composite Design. The effects of homogenisation and sonication times on entrapment efficiency (%EE) and drug release (%DR) were statistically analysed across nine batches. Particle size (PS) ranged from 302 ± 1.0 to 502 ± 2.0 nm, and zeta potential (ZP) from 25.8 ± 2.5 to 42.9 ± 1.7 mV. %EE and %DR (pH 1.2 for 2 h, then pH 7.4 for 22 h, 40 mL medium at 37 ± 0.5 °C) ranged from 69.32 ± 3.77 to 92.71 ± 0.16% and 19.24 ± 3.03 to 49.17 ± 1.98%, respectively. Optimised DTX nanoparticles (DNPs) showed EE of 78.18 ± 0.56%, DR of 46.21 ± 1.41% at 24 h, PS of 357.9 ± 2.4 nm, and ZP of 42.9 ± 3.7 mV. Scanning electron microscopy revealed ~300 nm cuboidal particles with smooth surfaces. X-Ray Diffraction and Differential Scanning Colorimetry confirmed reduced drug crystallinity in DNPs. In vitro haemolysis assays showed ~11.5-fold lower haemolytic potential (p < 0.0001) versus DTX, confirming improved safety. Fluorescence microscopy indicated enhanced cellular uptake of DNPs in MDA-MB-231 cells, while cytotoxicity assays of DNPs showed a lower IC50 (39.52 µM) compared to DTX (60.81 µM), demonstrating superior anticancer efficacy. Overall, DNPs represent a promising oral chemotherapy platform for breast cancer management.