Scientia Pharmaceutica

26 pages, 3919 KiB

Open AccessArticle

High Drug Loading of Amorphous Solid Dispersion by Hot Melt Extrusion: The Role of Magnesium Aluminometasilicate (Neusilin^® US2)

by Nithin Vidiyala, Pavani Sunkishala, Prashanth Parupathi, Preethi Mandati, Srujan Kumar Mantena, Raghu Rami Reddy Kasu and Dinesh Nyavanandi

Sci. Pharm. 2025, 93(3), 30; https://doi.org/10.3390/scipharm93030030 - 16 Jul 2025

Abstract

The objective of the current research is to investigate the role of Neusilin US2 as a porous carrier for improving the drug loading and stability of Ezetimibe (EZB) by hot melt extrusion (HME). The amorphous solid dispersions (ASDs) were developed from 10–40% of [...] Read more.

The objective of the current research is to investigate the role of Neusilin US2 as a porous carrier for improving the drug loading and stability of Ezetimibe (EZB) by hot melt extrusion (HME). The amorphous solid dispersions (ASDs) were developed from 10–40% of drug loading using Kollidon VA 64 (Copovidone) as a polymer matrix and Neusilin US2 as a porous carrier. The solid-state characterization of EZB was studied using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). The formulation blends were characterized for flow properties, and CTC (compressibility, tabletability, compactibility) profile. The in-vitro drug release profiles were studied in 0.1 N HCl (pH 1.2). The incorporation of Neusilin US2 has facilitated the development of ASDs up to 40% of drug loading. The CTC profile has demonstrated excellent tabletability for the ternary (EZB, copovidone and Neusilin) dispersions over binary dispersion (EZB and copovidone) formulations. The tablet formulations with binary (20%) and ternary (30% and 40%) dispersions have demonstrated complete dissolution of the drug in 30 min in 0.1 N HCl (pH 1.2). The incorporation of copovidone has prevented the recrystallization of the drug in the solution state. Upon storage of formulations at accelerated conditions, the stability of ternary dispersion tablets was preserved attributing to the entrapment of the drug within Neusilin pores thereby inhibiting molecular mobility. Based on the observations, the current research concludes that it is feasible to incorporate Neusilin US2 to improve the drug loading and stability of ASD systems. Full article

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10 pages, 2360 KiB

Open AccessCase Report

The New Frontier in Small-Cell Lung Cancer: Can Atezolizumab Ensure Enduring Stability?

by Stefano Notarangelo, Renato Lombardi, Massimo Lombardi, Giovanna Liguori, Marco Taurchini, Marco Sperandeo, Leonardo Specchiulli, Paola Conte, Fabrizia Checola, Emilia Langella, Antonio Giordano, Roberto Bava and Stefano Ruga

Sci. Pharm. 2025, 93(3), 29; https://doi.org/10.3390/scipharm93030029 - 5 Jul 2025

Abstract

Small-cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis despite initial responsiveness to chemotherapy. Platinum-based chemotherapy with etoposide has long been the standard first-line treatment, but recent advances in immunotherapy have improved outcomes. Phase III trials, including IMpower133 and CASPIAN, demonstrated [...] Read more.

Small-cell lung cancer (SCLC) is an aggressive malignancy with poor prognosis despite initial responsiveness to chemotherapy. Platinum-based chemotherapy with etoposide has long been the standard first-line treatment, but recent advances in immunotherapy have improved outcomes. Phase III trials, including IMpower133 and CASPIAN, demonstrated that adding immune checkpoint inhibitors, such as atezolizumab and durvalumab, to chemotherapy significantly enhances overall survival (OS) and progression-free survival (PFS). This case report describes a 76-year-old former smoker diagnosed with extensive-stage SCLC (ES-SCLC) following the detection of a left lower lung mass. The patient underwent combination therapy with carboplatin, etoposide, and atezolizumab, followed by maintenance atezolizumab. The patient demonstrated a sustained response to treatment, with significant tumor regression and no evidence of disease progression. Despite advanced age and comorbidities, treatment was well-tolerated, with no severe adverse events. Serial imaging over 24 months confirmed sustained disease stability, with regression of mediastinal lymphadenopathy and no new lesions. This case highlights the potential for prolonged disease control in select SCLC patients treated with chemo-immunotherapy. The absence of significant toxicities underscores the feasibility of immunotherapy even in elderly patients with comorbidities. These findings support the role of atezolizumab as a key component of ES-SCLC treatment and suggest the need for further research on predictors of durable response. Full article

(This article belongs to the Special Issue Monoclonal Antibodies in the Treatment of Diseases: Focus on Stability, Storage, and Administration)

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22 pages, 1889 KiB

Open AccessArticle

Development and Characterization of Bigels for the Topical Delivery of Curcumin

by Juan Luis Peréz-Salas, Martha Rocío Moreno-Jiménez, Luis Medina-Torres, Nuria Elizabeth Rocha-Guzmán, María Josefa Bernad-Bernad, Rubén Francisco González-Laredo and José Alberto Gallegos-Infante

Sci. Pharm. 2025, 93(3), 28; https://doi.org/10.3390/scipharm93030028 - 3 Jul 2025

Abstract

The topical application of curcumin can act directly on the tissue, but there are problems related to solubility and permeation. Bigels combine hydrogels and organogels to enhance the release and transport of bioactives through the skin. The aim of this study was to [...] Read more.

The topical application of curcumin can act directly on the tissue, but there are problems related to solubility and permeation. Bigels combine hydrogels and organogels to enhance the release and transport of bioactives through the skin. The aim of this study was to develop bigels for the topical delivery of curcumin. Employing a rheology test, it was found that all bigels showed a solid-like behavior structure (G′ > G″) with stiffness increasing with higher organogel content. The principle of time–temperature superposition (TTS) was used to generate master curves. Microscopy revealed a morphological structure that depended on the organogel/hydrogel ratio. The bigels exhibited a pH compatible with that of human skin, and the curcumin content met the standards for uniform dosage. Thermal characterization showed the presence of three peaks in coconut oil bigels and two peaks in castor oil bigels. Bigels with a 45% castor oil organogel/55% hydrogel ratio exhibited a longer controlled release of curcumin, while bigels with coconut oil showed a faster release. The release data were fitted to mathematical models indicating non-Fickian release. The permeability of curcumin through Strat-M membranes was investigated, and greater permeation was observed with increasing organogel content. The developed bigels could be a promising option for the topical delivery of curcumin. Full article

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16 pages, 1242 KiB

Open AccessArticle

Simultaneous Profiling of Terpenes and Cannabinoids in Hemp Essential Oils Using Static Headspace Gas Chromatography–Mass Spectrometry for Quality Control and Chemotype Differentiation

by Nathareen Chaiwangrach, Sirikan Mukda, Prapapan Temkitthawon, Nitra Nuengchamnong, Sarita Pinmanee, Thapakorn Somboon, Panatpong Boonnoun and Kornkanok Ingkaninan

Sci. Pharm. 2025, 93(2), 27; https://doi.org/10.3390/scipharm93020027 - 16 Jun 2025

Abstract

Hemp essential oils are rich in bioactive compounds, including terpenes and cannabinoids, yet standardized analytical methods for their simultaneous quality control are limited. This study aimed to (i) validate a static headspace gas chromatography–mass spectrometry (SHS-GC-MS) method for simultaneous quantification of 20 terpenes [...] Read more.

Hemp essential oils are rich in bioactive compounds, including terpenes and cannabinoids, yet standardized analytical methods for their simultaneous quality control are limited. This study aimed to (i) validate a static headspace gas chromatography–mass spectrometry (SHS-GC-MS) method for simultaneous quantification of 20 terpenes and 2 cannabinoids and (ii) apply it to fingerprint essential oils from four hemp strains, including local (HRDI2, HRDI5) and internationally cultivated (Charlotte’s Angel, Cherry Wine) varieties. The method met AOAC validation criteria, with detection limits of 0.025–0.5 µg/mL for terpenes and 1 µg/mL for cannabinoids. Quantitation limits ranged from 0.1–1 µg/mL for terpenes and 5 µg/mL for cannabinoids. Intraday precision (%RSD) ranged from 0.27–11.00%, while interday precision ranged from 3.14–13.89%. The method recoveries ranged from 85.12–115.47%. Precision and recovery confirmed the method’s reliability. Multivariate statistical analysis identified 82 metabolites, revealing distinct chemical fingerprints among strains, and emerged as newly identified chemotype markers, supporting chemotype classification. This work demonstrates, for the first time, a solvent-free, automatable SHS-GC-MS approach for simultaneous terpene and cannabinoid profiling in hemp essential oils, enabling both qualitative and quantitative characterization and supporting regulatory compliance for the development of standardized phytopharmaceutical products. Full article

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24 pages, 2661 KiB

Open AccessReview

Oral Small-Molecule GLP-1 Receptor Agonists: Mechanistic Insights and Emerging Therapeutic Strategies

by Héctor Iván Saldívar-Cerón, Jorge Arturo Vargas-Camacho, Sonia León-Cabrera, Paola Briseño-Díaz, Ari Evelyn Castañeda-Ramírez, Axel Eduardo Muciño-Galicia and María Regina Díaz-Domínguez

Sci. Pharm. 2025, 93(2), 26; https://doi.org/10.3390/scipharm93020026 - 11 Jun 2025

Abstract

Small-molecule glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent an innovative advancement in oral therapeutics, addressing key limitations associated with injectable peptide-based incretin therapies. These nonpeptidic agents exert their actions primarily through non-canonical binding orthosteric sites within the GLP-1 receptor transmembrane domain, enabling selective G [...] Read more.

Small-molecule glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent an innovative advancement in oral therapeutics, addressing key limitations associated with injectable peptide-based incretin therapies. These nonpeptidic agents exert their actions primarily through non-canonical binding orthosteric sites within the GLP-1 receptor transmembrane domain, enabling selective G protein (Gs)-biased signaling with reduced β-arrestin-mediated adverse effects. Orforglipron has notably advanced through Phase 3 clinical development, demonstrating significant reductions in hemoglobin A1c and body weight (up to 7.9%) with favorable tolerability. Conversely, promising candidates such as danuglipron and lotiglipron were discontinued due to hepatotoxicity, underscoring critical safety concerns intrinsic to small-molecule GLP-1RA development. Current clinical candidates, including GSBR-1290, CT-996, and ECC5004, continue to offer substantial potential due to their oral bioavailability, simplified dosing regimens, and favorable gastrointestinal tolerability. Nevertheless, challenges persist regarding hepatic safety, pharmacodynamic variability, and limited long-term outcome data. This review integrates current structural, pharmacological, and clinical evidence, highlights key mechanistic innovations—including biased agonism, covalent binding strategies, and allosteric modulation—and discusses future directions for this rapidly evolving therapeutic class in metabolic disease management. Full article

(This article belongs to the Topic Research in Pharmacological Therapies, 2nd Edition)

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16 pages, 3929 KiB

Open AccessArticle

Prenylated Chalcones as Anticancer Agents Against Castration-Resistant Prostate Cancer

by Marcos Morales-Reyna, Elisa Elvira Figueroa-Angulo, José Espinoza-Hicks, Alejandro Camacho-Dávila, César López-Camarillo, Laura Isabel Vázquez-Carrillo, Alfonso Salgado-Aguayo, Ángeles Carlos-Reyes, Violeta Deyanira Álvarez-Jiménez, Jonathan Puente-Rivera and María Elizbeth Alvarez-Sánchez

Sci. Pharm. 2025, 93(2), 25; https://doi.org/10.3390/scipharm93020025 - 5 Jun 2025

Abstract

Prenylated chalcones have garnered attention as potential anticancer agents due to their ability to modulate multiple cancer-related pathways. In this study, we synthesized and evaluated nine novel prenylated chalcone derivatives for their antiproliferative effects against castration-resistant prostate cancer (CRPC) cell lines, DU145 and [...] Read more.

Prenylated chalcones have garnered attention as potential anticancer agents due to their ability to modulate multiple cancer-related pathways. In this study, we synthesized and evaluated nine novel prenylated chalcone derivatives for their antiproliferative effects against castration-resistant prostate cancer (CRPC) cell lines, DU145 and PC3. Among these, compounds 6d and 7j demonstrated potent cytotoxic activity, with IC₅₀ values comparable to cisplatin, and exhibited selective toxicity towards cancer cells over non-tumorigenic RWPE-1 cells. Mechanistic investigations revealed that these compounds induce apoptosis via mitochondrial membrane depolarization and increased late apoptotic events. Flow cytometry confirmed activation of both early and late apoptotic pathways. These findings highlight the potential of chalcone derivatives 6d and 7j as promising therapeutic candidates for CRPC treatment and support further development of chalcone-based molecules in precision oncology. Full article

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23 pages, 1868 KiB

Open AccessArticle

Application of Lactose Co-Processed Excipients as an Alternative for Bridging Pharmaceutical Unit Operations: Manufacturing an Omeprazole Tablet Prototype via Direct Compression

by Raymar Andreina Lara Garcia, Jesús Alberto Afonso Urich, Andreina Isabel Afonso Urich, Dalibor Jeremic and Johannes Khinast

Sci. Pharm. 2025, 93(2), 24; https://doi.org/10.3390/scipharm93020024 - 28 May 2025

Abstract

Improving the manufacturability of drug formulations via direct compression has been of great interest for the pharmaceutical industry. Selecting excipients plays a vital role in obtaining a high-quality product without the wet granulation processing step. In particular, for diluents which are usually present [...] Read more.

Improving the manufacturability of drug formulations via direct compression has been of great interest for the pharmaceutical industry. Selecting excipients plays a vital role in obtaining a high-quality product without the wet granulation processing step. In particular, for diluents which are usually present in a larger amount in a formulation, choosing the correct one is of utmost importance in the production of tablets via any method. In this work, we assessed the possibility of manufacturing a small-molecule drug product, omeprazole, which has been historically manufactured via a multi-step processes such as wet granulation and multiple-unit pellet system (MUPS). For this purpose, four prototypes were developed using several diluents: a co-processed excipient (Microcelac^®), two granulated forms of alpha-lactose monohydrate (Tablettose^® 70 and Tabletose^® 100), and a preparation of microcrystalline cellulose (Avicel^® PH102) and lactose (DuraLac^® H), both of which are common excipients without any enhancement. The tablets were produced using a single punch tablet press and thoroughly characterized physically and chemically in order to assess their functionality and adherence to drug product specifications. The direct compression process was used for the manufacturing of all proposed formulations, and the prototype formulated using Microcelac^® showed the best results and performance during the compression process. In addition, it remained stable over twelve months under 25 °C/60% RH conditions. Full article

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21 pages, 1003 KiB

Open AccessArticle

Alpinia zerumbet Extract Mitigates PCB 126-Induced Neurotoxicity and Locomotor Impairment in Adult Male Mice

by Paula Hosana Fernandes da Silva, Jemima Isnardo Fernandes, Matheus Pontes de Menezes, Fabrícia Lima Fontes-Dantas, André Luiz Nunes Freitas, Rayane Efraim Correa, Ulisses Cesar de Araujo, Dayane Teixeira Ognibene, Cristiane Aguiar da Costa, Cláudio Carneiro Filgueiras, Alex Christian Manhães, Júlio Beltrame Daleprane, Angela de Castro Resende and Graziele Freitas de Bem

Sci. Pharm. 2025, 93(2), 23; https://doi.org/10.3390/scipharm93020023 - 25 May 2025

Abstract

Polychlorinated biphenyls (PCBs) are synthetic chemical compounds that have bioaccumulated and contaminated the entire global ecosystem, causing neurotoxic effects. However, polyphenols may have protective effects against this neurotoxicity. We aimed to investigate the neuroprotective effect of a hydroalcoholic extract of fresh leaves of [...] Read more.

Polychlorinated biphenyls (PCBs) are synthetic chemical compounds that have bioaccumulated and contaminated the entire global ecosystem, causing neurotoxic effects. However, polyphenols may have protective effects against this neurotoxicity. We aimed to investigate the neuroprotective effect of a hydroalcoholic extract of fresh leaves of Alpinia zerumbet (ALE), which is rich in polyphenols, on the neurobehavioral changes induced by 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126). We divided C57BL/6 male mice into four groups (n = 40): Control, Control + ALE, PCB, and PCB + ALE. We administered the ALE (50 mg/kg/day) through drinking water and PCB 126 (2 mg/kg/once a week) intraperitoneally for four weeks. The mice were subjected to the elevated plus maze (EPM) and open field (OF) tests in the last week of treatment. PCB 126 reduced locomotor activity, DOPAC levels, dopamine turnover, and D2 receptor expression. This compound also increased lipid peroxidation, tyrosine levels, and BAX expression in the cerebral cortex. Notably, ALE treatment prevented locomotor activity reduction and increased DOPAC levels, dopamine turnover, and D2 receptor expression. Moreover, the extract prevented the PCB-induced increases in BAX expression and lipid peroxidation. Finally, the ALE increased SOD antioxidant activity. Our investigation highlights that using the ALE may serve as a therapeutic strategy against PCB-induced neurotoxicity. Full article

(This article belongs to the Topic Natural Products and Drug Discovery—2nd Edition)

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20 pages, 4884 KiB

Open AccessReview

Antibacterial Activity of Metal Complexes of Cu(II) and Ni(II) with the Ligand 2-(Phenylsubstituted) Benzimidazole

by Ivone Vanessa Mañozca-Dosman, Alberto Aragón-Muriel and Dorian Polo-Cerón

Sci. Pharm. 2025, 93(2), 22; https://doi.org/10.3390/scipharm93020022 - 16 May 2025

Abstract

Benzimidazoles are considered a promising class of bioactive heterocyclic compounds that show a wide variety of useful biological properties due to their structural similarities to nucleotides such as purines. Among these properties, great attention has been given to the antibacterial activity exhibited by [...] Read more.

Benzimidazoles are considered a promising class of bioactive heterocyclic compounds that show a wide variety of useful biological properties due to their structural similarities to nucleotides such as purines. Among these properties, great attention has been given to the antibacterial activity exhibited by molecules containing a benzimidazole nucleus in their structure since recent research results have shown the potential of such molecules as alternatives in the fight against bacterial resistance. When these compounds have phenylsubstituted groups in the 2-position of the imidazole ring, a series of molecules can be obtained with generally improved pharmacological activity. These types of compounds are suitable for the formation of stable complexes with several transition metals, including nickel and copper; such compounds have also exhibited many biological properties in different reports. Accordingly, this brief review focuses on recent work on the synthesis and characterization of metal complexes of Ni(II) and Cu(II) with ligands derived from 2-(phenylsubstituted) benzimidazole that were subsequently evaluated for antibacterial activity. Full article

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12 pages, 2318 KiB

Open AccessArticle

Radioprotective Efficacy of Phosphorus-Containing Polymer Complexes of Amifostine WR-2721

by Ivelina Tsacheva and Dzhamal Uzun

Sci. Pharm. 2025, 93(2), 21; https://doi.org/10.3390/scipharm93020021 - 29 Apr 2025

Abstract

Background: The aim of this study was to investigate the radioprotective efficacy of polymer complexes constructed from amifostine (WR-2721) and poly(hydroxyoxyethylene phosphate)s with different molecular weights. The use of suitable polymers for the immobilization of radioprotective drugs is aimed at improving or obtaining [...] Read more.

Background: The aim of this study was to investigate the radioprotective efficacy of polymer complexes constructed from amifostine (WR-2721) and poly(hydroxyoxyethylene phosphate)s with different molecular weights. The use of suitable polymers for the immobilization of radioprotective drugs is aimed at improving or obtaining important new properties. Methods: The radioprotective efficacy of the compounds was investigated by cytotoxicity and the survival of mouse embryonic fibroblasts MEF LIG4^+/+ and MEF LIG4^−/− cells irradiated with 2, 6 and 12 Gy in the presence of amifostine (WR-2721) and its polymer complexes. Results: The radioprotective efficacy of the polymer complexes constructed of amifostine (WR-2721) and poly(hydroxyoxyethylene phosphate)s with different molecular weights showed promising activity and dose regimens. Conclusions: Cytotoxicity studies for tested cell lines MEF LIG4^+/+ and MEF LIG4^−/− cells showed that the polymer complexes were not toxic when equivalent doses of the drug amifostine (WR-2721) were applied to the cells. Irradiated MEF LIG4^+/+ cells demonstrated an increase in the surviving fraction when pre-treated with 0.5–5 mM polymer complexes when equivalent doses of amifostine (WR-2721) were applied to the cells and irradiated. The radioprotective efficacy had increased when the cells MEF LIG4^+/+ were irradiated with 12 Gy. These findings demonstrate that poly(hydroxyoxyethylene phosphate)s are suitable carriers of the radioprotective drug amifostine (WR-2721). They further suggest that they may be interesting for researchers seeking new challenges in discovering advanced radioprotective active substances. Full article

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18 pages, 1887 KiB

Open AccessArticle

Comparative Analysis of Adverse Effects: Protein Kinase Inhibitors Versus Traditional Anticancer Therapies

by Ioana Lavinia Radulian, Georgiana Nitulescu, Anca Zanfirescu and George Mihai Nitulescu

Sci. Pharm. 2025, 93(2), 20; https://doi.org/10.3390/scipharm93020020 - 21 Apr 2025

Abstract

The adverse effects of protein kinase inhibitors (PKIs) and other anticancer therapies were compared using FDA Adverse Events Reporting System (FAERS) data. The dataset included 159 FDA-approved anticancer drugs (71 PKIs, 88 nonPKIs) and analyzed 8216 unique adverse event (AE) terms. PKIs showed [...] Read more.

The adverse effects of protein kinase inhibitors (PKIs) and other anticancer therapies were compared using FDA Adverse Events Reporting System (FAERS) data. The dataset included 159 FDA-approved anticancer drugs (71 PKIs, 88 nonPKIs) and analyzed 8216 unique adverse event (AE) terms. PKIs showed fewer systemic toxicities, with an average of 230.1 distinct AEs per drug, compared to 537.7 in nonPKIs. Hematologic AEs were significantly lower in PKIs (e.g., febrile neutropenia: 1.93% vs. 5.25%; thrombocytopenia: 2.18% vs. 3.87%), coupled with a lower incidence of infections (6.87% vs. 14.2%) and immunosuppressive effects. However, gastrointestinal and skin-related AEs were more common in PKIs (e.g., diarrhea: 13.95% vs. 8.36%). A higher proportion AEs in the PKI group (14.57%) were classified under “Investigations”, compared to the nonPKI group (9.87%). The frequency of “Skin and subcutaneous tissue disorders” AEs was twice as high in the PKI group. Clustering analysis grouped drugs by AE profiles, showing that PKIs formed more homogeneous clusters, while nonPKIs had broader variability. Multi-kinase inhibitors with VEGFR activity were linked to dermatologic AEs, likely due to EGFR inhibition in basal keratinocytes. Despite PKIs’ targeted mechanisms, resistance remains a challenge, requiring biomarker-driven strategies. This study highlights PKIs’ improved tolerability but emphasizes using personalized treatment approaches to optimize efficacy and safety. Full article

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16 pages, 3233 KiB

Open AccessArticle

Study of the Influence of Pharmaceutical Excipients on the Solubility and Permeability of BCS Class II Drugs

by Vivien Bárdos, Rita Szolláth, Petra Tőzsér, Arash Mirzahosseini, Bálint Sinkó, Réka Angi and Krisztina Takács-Novák

Sci. Pharm. 2025, 93(2), 19; https://doi.org/10.3390/scipharm93020019 - 11 Apr 2025

Abstract

Most novel active pharmaceutical ingredients have low water solubility; therefore, solubility-enhancing methods are applied. The aim of the present investigation is to study the impact of nine commonly used pharmaceutical excipients (fillers, surfactants, cyclodextrins, polymers) on solubility, permeability and their relationship. This is [...] Read more.

Most novel active pharmaceutical ingredients have low water solubility; therefore, solubility-enhancing methods are applied. The aim of the present investigation is to study the impact of nine commonly used pharmaceutical excipients (fillers, surfactants, cyclodextrins, polymers) on solubility, permeability and their relationship. This is crucial for ensuring optimal bioavailability. Carbamazepine, naproxen and pimobendan were chosen as model compounds due to their different acid–base properties. Equilibrium solubility was measured by the traditional shake flask method. Effective permeability was determined by the PAMPA model. Measurements of ionizable compounds were carried out at three pH values. The pH-dependent change in the investigated parameters is maintained even in the presence of excipients. Fillers resulted in a slight or no effect, while the impact of other excipients showed a significant concentration dependence. The impact of excipients was influenced by the structure and ionization state of the molecules. The dominance of the ionized form moderates the impact of excipients. The changes in solubility were more pronounced than in the case of permeability. By examining the effect of the ionization state and interactions with excipients, this work supports the development of formulations that enhance solubility with minimal impacts on permeability. Additionally, it can serve as good basis for preformulation studies and design optimization. Full article

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34 pages, 771 KiB

Open AccessReview

Polygenic Risk Scores for Personalized Cardiovascular Pharmacogenomics―A Scoping Review

by Aaryan Dwivedi, Jobanjit S. Phulka, Peyman Namdarimoghaddam and Zachary Laksman

Sci. Pharm. 2025, 93(2), 18; https://doi.org/10.3390/scipharm93020018 - 8 Apr 2025

Abstract

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, often involving a strong genetic background. Polygenic risk scores (PRSs) combine the cumulative effects of multiple genetic variants to quantify an individual’s susceptibility to CVD. Pharmacogenomics (PGx) can further personalize treatment by tailoring [...] Read more.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, often involving a strong genetic background. Polygenic risk scores (PRSs) combine the cumulative effects of multiple genetic variants to quantify an individual’s susceptibility to CVD. Pharmacogenomics (PGx) can further personalize treatment by tailoring medication choices to an individual’s genetic profile. Even with these potential benefits, the extent to which PRS can be integrated into the PGx of CVD remains unclear. Our review provides an overview of current evidence on the application of PRS in the PGx of CVD, examining clinical utility and limitations and providing directions for future research. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews protocol, we conducted a comprehensive literature search in PubMed, EMBASE, and the Web of Science. Studies investigating the relationship between PRS in predicting the efficacy, adverse effects, or cost-effectiveness of cardiovascular medications were selected. Of the 1894 articles identified, 32 met the inclusion criteria. These studies predominantly examined lipid-lowering therapies, antihypertensives, and antiplatelets, although other medication classes (e.g., rate-control drugs, ibuprofen/acetaminophen, diuretics, and antiarrhythmics) were also included. Our findings showed that PRS is most robustly validated in lipid-lowering therapies, especially statins, where studies reported that individuals with higher PRSs derived the greatest reduction in lipids while on statins. Studies analyzing antihypertensives, antiplatelets, and antiarrhythmic medications demonstrated more variable outcomes, though certain PRSs did identify subgroups with significantly improved response rates or a higher risk of adverse events. Though PRS was a strong tool in many cases, we found some key limitations in its applicability in research, such as the under-representation of non-European-ancestry cohorts in the examined studies and a lack of standardized outcome reporting. In conclusion, though PRS offers promise in improving the efficacy of PGx of CVD by enhancing the personalization of medication on an individual level, several obstacles, such as the need for including a broader ancestral diversity and more robust cost-effectiveness data remain. Future research must (i) prioritize validating PRS in ethnically diverse populations, (ii) refine PRS derivation methods to tailor them for drug response phenotypes, and (iii) establish clear and attainable guidelines for standardizing the reporting of outcomes. Full article

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14 pages, 2359 KiB

Open AccessArticle

Pregestational Stress Representing a Maternal Depression Model and Prenatally Applied Antidepressant Mirtazapine Modulate Hippocampal Excitability in Offspring

by Lucia Dubiel-Hoppanova, Alzbeta Filipova, Stanislava Bukatova, Katarina Ondacova, Matus Tomko, Bohumila Jurkovicova-Tarabova, Michal Dubovicky, Eliyahu Dremencov and Lubica Lacinova

Sci. Pharm. 2025, 93(2), 17; https://doi.org/10.3390/scipharm93020017 - 31 Mar 2025

Abstract

Maternal depression negatively affects the neurodevelopment of offspring, but its pharmacological treatment during gestation remains controversial. This study reports the consequences of maternal depression and/or prenatal antidepressant treatment with mirtazapine on offspring early neurodevelopment via an animal model of maternal depression induced by [...] Read more.

Maternal depression negatively affects the neurodevelopment of offspring, but its pharmacological treatment during gestation remains controversial. This study reports the consequences of maternal depression and/or prenatal antidepressant treatment with mirtazapine on offspring early neurodevelopment via an animal model of maternal depression induced by pregestational chronic unpredictable stress (CUS). Offspring from four groups were studied: nonstressed vehicle-treated dams, nonstressed mirtazapine-treated dams, stressed vehicle-treated dams, and stressed mirtazapine-treated dams. The hippocampal excitability of offspring was examined in primary hippocampal cultures established on the first postnatal day, reflecting mostly prenatal development, and in hippocampal slices prepared on postnatal days 11–13, reflecting an early postnatal development. The pregestational CUS modeling of maternal depression moderately suppressed offspring hippocampal excitability in primary cultures but facilitated it in slices. Mirtazapine administered to CUS-exposed dams partly rectified the changes observed in primary cultures of pups from untreated dams and, more prominently, in slices. Mirtazapine itself negatively affected the hippocampal excitability of nonstressed dam offspring in primary culture, and this effect was diminished in slices. Since altered hippocampal neurotransmission might be responsible, at least in part, for the neuropsychopathologies frequently observed in the offspring of depressed mothers, and mirtazapine was able to partly relieve such changes, this treatment may be also beneficial during the prenatal and perinatal periods. Full article

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16 pages, 6539 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Some Coumarin–Triazole Conjugates as Potential Anticancer Agents

by Anarkul S. Kishkentayeva, Mohammad Saleh Hamad, Mikhail A. Pokrovsky, Zhanar R. Shaimerdenova, Aigerim S. Adekenova, Gulnara K. Mambeterzina, Victor A. Savelyev, Andrey G. Pokrovsky and Elvira E. Shults

Sci. Pharm. 2025, 93(2), 16; https://doi.org/10.3390/scipharm93020016 - 31 Mar 2025

Cited by 1

Abstract

Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes, the development of compounds with higher anticancer efficacy and a lower level of side effects is an important task in modern pharmaceutical chemistry. Herein, a mild and convenient method for [...] Read more.

Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes, the development of compounds with higher anticancer efficacy and a lower level of side effects is an important task in modern pharmaceutical chemistry. Herein, a mild and convenient method for the preparation of N1-substituted 3-(1,2,3-triazolyl-methoxycarbonyl)coumarins or bis(coumarine-3-carboxylate)bis(triazole)alkandiyl by the copper(I)-catalyzed Huisgen cycloaddition reaction of readily available coumarin-3-carboxylic acid propynyl ester with azides or diazides has been presented. The synthesized compounds have been tested for their cytotoxicity on various cancer and noncancerous cell lines using the MTT assay. All new compounds were nontoxic on normal epithelial VERO cells. Two derivatives exhibited selectivity towards HPV-negative human cervical cancer cells, C33 A, with excellent activities in low concentrations (GI₅₀ 4.4–7.0 µM). In vitro mechanistic studies showed that bis(coumarine)bis(triazolylester) conjugate 3 induced time-dependent apoptosis in cervical cancer cell lines C33 A and CaSki, at the GI₅₀ concentration, as measured by Annexin V-FITC/PI staining. The most active coumarin–triazolyl ester conjugate 2g possessed anticancer activities, as indicated by its ability to induce S/G2 phase cell cycle arrest at a low concentration and early apoptosis in CaSki cells. The obtained results revealed the potential of new compounds as anticancer agents, particularly against cervical cancer. Full article

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13 pages, 1711 KiB

Open AccessArticle

Wild Harvesting vs. Cultivation: Total Petasin Content in Petasites hybridus Rhizome Extracts Determines Spasmolytic Effects

by Christiane Halbsguth, Verena M. Merk, Jürgen Drewe, Georg Boonen and Veronika Butterweck

Sci. Pharm. 2025, 93(2), 15; https://doi.org/10.3390/scipharm93020015 - 21 Mar 2025

Abstract

The use of herbal medicines containing Petasites hybridus extracts has a long history in the treatment of various ailments. The observed effects are primarily due to pharmacologically active compounds such as petasin, isopetasin, and neopetasin. In evidence-based phytotherapy, extracts from leaves and rhizomes [...] Read more.

The use of herbal medicines containing Petasites hybridus extracts has a long history in the treatment of various ailments. The observed effects are primarily due to pharmacologically active compounds such as petasin, isopetasin, and neopetasin. In evidence-based phytotherapy, extracts from leaves and rhizomes are applied for different indications. While leaf extracts are administered to treat allergic rhinitis symptoms, rhizome extracts are utilized among others in the management of gastrointestinal spasms and migraines. The quality and source of plants are critical for producing authorized herbal medicinal products. Although the preparation of P. hybridus leaf extracts from cultivated plant material is already established, the rhizomes used for preparing extracts are still derived from commercial wild collections. However, switching to cultivation is desirable to ensure consistent quality and availability. For regulatory purposes, comparative pharmacological studies are needed to assess the bioactivity of plant material from different sources. Therefore, this study analyzed rhizome extracts from wild harvesting and cultivation for their petasin composition (i.e., isopetasin, neopetasin, petasin) and spasmolytic effects on Ca²⁺-dependent precontracted guinea pig ileum ex vivo. The results confirm petasins as active compounds of P. hybridus rhizome extracts. Moreover, they demonstrate that the total content of petasins determines the spasmolytic effects, regardless of the individual composition of the different petasins. No significant differences in efficacy were found between cultivated and wild-collected rhizomes, demonstrating that cultivated material is a reliable, consistent, and sustainable alternative for P. hybridus rhizome extract production. Full article

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16 pages, 1447 KiB

Open AccessReview

Formulations with Boric Acid or Aryl-Organoboron Compounds for Treating Diabetic Foot Ulcers

by Marvin A. Soriano-Ursúa, Marlet Martínez-Archundia, Ahmet Kilic, Teresa Pérez-Capistran, Miriam A. Hernández-Zamora, Juan E. López-Ramos and Eunice D. Farfán-García

Sci. Pharm. 2025, 93(1), 14; https://doi.org/10.3390/scipharm93010014 - 19 Mar 2025

Abstract

Boron-containing compounds (BCCs) have been proposed for the treatment of diabetes and its complications. Recent studies have reported an improvement in the design and development of pharmaceutical formulations (often gels) containing boric acid applied to the foot ulcers of humans diagnosed with diabetes. [...] Read more.

Boron-containing compounds (BCCs) have been proposed for the treatment of diabetes and its complications. Recent studies have reported an improvement in the design and development of pharmaceutical formulations (often gels) containing boric acid applied to the foot ulcers of humans diagnosed with diabetes. The proposed mechanisms of action of boric acid include antimicrobial effects, the modulation of inflammation and metabolism, and the induction of cell differentiation. On the other hand, recent studies have suggested that boronic acids are potent antibacterial and antifungal compounds, effective modulators of inflammation, and inducers of vascular regeneration as well as inducers of healing, and they confer attractive properties such as adhesion, interaction, and the formation of complexes in formulations. Moreover, only a handful of studies conducted in animals have suggested the effective role of some BCCs as potent enhancers of wound healing, including their actions on induced and/or infected wounds in animals with disrupted metabolism. Also, it should be mentioned that no strong interactions between boric acid and the boronic acids present in formulations have been described. The developed combination could act as an additive and complementary therapy in the treatment of diabetic ulcers in humans. Further studies are required to support the hypothesis that this combination acts through diverse mechanisms to improve healing while avoiding or limiting a local or disseminated infection. Furthermore, the safety of BCCs used for foot ulcers should be established, as should the role of these formulations as a complementary therapy in current protocols for treating patients with diabetic foot ulcers. Full article

(This article belongs to the Topic New Compounds Discovery and Development in Medicine — Advances in Research on Potential Therapeutic Agents and Drug Candidates, 2nd Edition)

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29 pages, 1152 KiB

Open AccessReview

Physicochemical Characteristics of Cardiological Drugs and Practical Recommendations for Intravenous Administration: A Systematic Review

by Massimiliano Quici, Elena Martini, Davide Giustivi, Maria Calloni, Chiara Cogliati, Alba Taino, Antonella Foschi, Andrea Gori, Paolo Zappa, Francesco Casella, Arianna Bartoli, Leyla La Cava, Alessia Meschia, Rosita Celano, Francesco Urso, Dario Cattaneo and Antonio Gidaro

Sci. Pharm. 2025, 93(1), 13; https://doi.org/10.3390/scipharm93010013 - 12 Mar 2025

Abstract

Most cardiological drugs need intravenous administration to have a fast effect in an emergency. Intravenous administration is linked to complications, such as tissue infiltration and thrombophlebitis. Aiming to supply an effective tool for the development of appropriate policies, this systematic review provides practical [...] Read more.

Most cardiological drugs need intravenous administration to have a fast effect in an emergency. Intravenous administration is linked to complications, such as tissue infiltration and thrombophlebitis. Aiming to supply an effective tool for the development of appropriate policies, this systematic review provides practical recommendations about the diluent, pH, osmolarity, dosage, vesicant properties, and phlebitis rate of the most commonly used cardiological drugs evaluated in randomized controlled trials (RCTs) till 31 August 2024. The authors searched for available IV cardiological drugs in RCTs in PUBMED EMBASE^®, EBSCO-CINAHL^®, and Cochrane Controlled Clinical trials. Drugs’ chemical features were obtained online, in drug data sheets, and in scientific papers, establishing that the drugs with a pH of <5 or >9, an osmolarity > 600 mOsm/L, and a high incidence of phlebitis reported in the literature, as well as vesicant drugs, require utmost caution during administration. A total of 857 papers were evaluated and 316 studies were included. A total of 84 cardiological drugs were identified, of which only 31 (37%) can be safely infused via a peripheral route. Thrombolytics and anticoagulants are considered the safest classes of drugs, with only one drug flagged as a “red flag” medication. However, a higher percentage of drugs in other categories meet the “red flag” criteria, including antiarrhythmics (52%), antiplatelet agents (67%), diuretics (67%), antihypertensives (70%), other drugs (77%), and vasoconstrictors and inotropics (89%). Understanding the physicochemical properties of cardiological drugs is essential for significantly improving patient safety and preventing administration errors and local side effects. Full article

(This article belongs to the Topic Challenges and Opportunities in Drug Delivery Research)

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18 pages, 11514 KiB

Open AccessArticle

Exploring Cannabidiol’s Therapeutic Role in Colorectal Cancer: Network Pharmacology and Molecular Docking Insights

by Juan Manuel Guzmán-Flores, Fernando Martínez-Esquivias, Antistio Alviz-Amador, Guadalupe Thonanzyn Avilés-Rodríguez and Michel Fabricio García-Azuela

Sci. Pharm. 2025, 93(1), 12; https://doi.org/10.3390/scipharm93010012 - 28 Feb 2025

Abstract

Background: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, and current treatments have significant side effects. Cannabidiol (CBD), a compound derived from Cannabis sativa, has demonstrated promising anticancer properties. However, further investigation is required to elucidate its underlying molecular [...] Read more.

Background: Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, and current treatments have significant side effects. Cannabidiol (CBD), a compound derived from Cannabis sativa, has demonstrated promising anticancer properties. However, further investigation is required to elucidate its underlying molecular mechanisms. Methods: Network pharmacology and molecular docking analysis approaches were utilized. Molecular targets of CBD and CRC-associated genes were identified using the Swiss Target Prediction, Malacards, and DisGeNet databases. Protein–protein interactions were analyzed using the STRING and Cytoscape. Ontology enrichment was conducted using ShinyGO, and gene expression and immune infiltration were evaluated with UALCAN and TISIDB. Results: We found 95 common genes between CRC and CBD targets. Six major genes (ANXA5, IGF1R, JAK2, MAPK8, MDM2, and PARP1) were particularly interesting due to their high connectivity and role in relevant metabolic pathways. The results of the molecular docking analysis indicated that CBD interacts favorably with these genes, modulating critical pathways such as RAS/MAPK and PI3K-AKT/FoxO, which are involved in cell proliferation, apoptosis, and cell cycle regulation. ANXA5 and JAK2 were identified as particularly relevant, as they correlated significantly with immune cell infiltration, suggesting a role in the immunoregulation of the tumor microenvironment. Conclusions: CBD has the potential to modulate key molecular processes in CRC through specific pathways and core genes, presenting itself as a possible complementary therapy to improve efficacy and reduce the adverse effects of conventional treatments. Full article

(This article belongs to the Topic Bioinformatics in Drug Design and Discovery—2nd Edition)

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