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Sci. Pharm., Volume 93, Issue 3 (September 2025) – 8 articles

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16 pages, 7856 KiB  
Review
Risks of Oral Anticoagulants: Interactions with Drugs and Medicinal Plants
by Ana Sofia Martins, Cristina Monteiro and Ana Paula Duarte
Sci. Pharm. 2025, 93(3), 35; https://doi.org/10.3390/scipharm93030035 - 30 Jul 2025
Abstract
Oral anticoagulants, including warfarin, a vitamin K antagonist, have been used for anticoagulation therapy, but their limitations, such as drug interactions and complex dosing, have prompted the development of direct oral anticoagulants (DOACs) like rivaroxaban, apixaban, dabigatran, and edoxaban. This study reviews the [...] Read more.
Oral anticoagulants, including warfarin, a vitamin K antagonist, have been used for anticoagulation therapy, but their limitations, such as drug interactions and complex dosing, have prompted the development of direct oral anticoagulants (DOACs) like rivaroxaban, apixaban, dabigatran, and edoxaban. This study reviews the interactions of both warfarin and DOACs, particularly those influenced by cytochrome P450 enzymes and P-glycoprotein. Warfarin is metabolized by various cytochrome P450 isoforms, making it vulnerable to interactions with medications and herbs that modulate these enzymes. In contrast, DOACs, while having fewer interactions, are still affected by strong inducers or inhibitors of cytochrome 3A4 and P-glycoprotein, depending on the specific drug. Some herbs may also interfere with these pathways. Continuous monitoring of these interactions is crucial to ensure the safe use of oral anticoagulants. The findings underscore the importance of identifying and understanding these interactions to improve patient safety and guide appropriate anticoagulant therapy. Full article
26 pages, 685 KiB  
Article
Novel Research Regarding Topical Use of Diclofenac in Dermatology—Non-Clinical and Clinical Data
by Diana Ana-Maria Nițescu, Horia Păunescu, Mihnea Costescu, Bogdan Nițescu, Laurențiu Coman, Ion Fulga and Oana Andreia Coman
Sci. Pharm. 2025, 93(3), 34; https://doi.org/10.3390/scipharm93030034 - 30 Jul 2025
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Abstract
Diclofenac, an aryl-acetic acid derivative from the non-steroidal anti-inflammatory drug class, is the subject of multiple non-clinical and clinical studies regarding its usefulness in treating some dermatologic pathologies with an inflammatory, auto-immune, or proliferative component. Diclofenac is now approved for the topical treatment [...] Read more.
Diclofenac, an aryl-acetic acid derivative from the non-steroidal anti-inflammatory drug class, is the subject of multiple non-clinical and clinical studies regarding its usefulness in treating some dermatologic pathologies with an inflammatory, auto-immune, or proliferative component. Diclofenac is now approved for the topical treatment of actinic keratoses (AK), pre-malignant entities that have the risk of transformation into skin carcinomas. The hypothesis that diclofenac increases granular layer development in the mice tail model, having an anti-psoriatic effect, was demonstrated in a previous study in which 1% and 2% diclofenac ointment was evaluated. The aim of the present study was to perform experimental research on the topical effect of diclofenac in the mice tail model, by testing 4% and 8% diclofenac ointment, which is presented in the first part of the manuscript. In the second part of the manuscript, we also aimed to conduct a literature review regarding topical diclofenac uses in specific dermatological entities by evaluating the articles published in PubMed and Scopus databases during 2014–2025. The studies regarding the efficacy of topical diclofenac in dermatological diseases such as AK and field cancerization, actinic cheilitis, basal cell carcinoma, Bowen disease, Darier disease, seborrheic keratoses, and porokeratosis, were analyzed. The results of the experimental work showed a significant effect of 4% and 8% diclofenac ointment on orthokeratosis degree when compared to the negative control groups. Diclofenac in the concentration of 4% and 8% significantly increased the orthokeratosis degree compared to the negative control with untreated mice (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test) and to the negative control with vehicle (p = 0.006 and p = 0.011, respectively, using the Kruskal–Wallis test). The mean epidermal thickness was increased for the diclofenac groups, but not significantly when compared to the control groups. The results are concordant with our previous experiment, emphasizing the need for future clinical trials on the use of topical diclofenac in psoriasis. Full article
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12 pages, 1311 KiB  
Review
Modulation of Voltage-Gated Na+ Channel Currents by Small Molecules: Effects on Amplitude and Gating During High-Frequency Stimulation
by Cheng-Yuan Lin, Zi-Han Gao, Chi-Wai Cheung, Edmund Cheung So and Sheng-Nan Wu
Sci. Pharm. 2025, 93(3), 33; https://doi.org/10.3390/scipharm93030033 - 24 Jul 2025
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Abstract
Cumulative inhibition of voltage-gated Na+ channel current (INa) caused by high-frequency depolarization plays a critical role in regulating electrical activity in excitable cells. As discussed in this review paper, exposure to certain small-molecule modulators can perturb INa during [...] Read more.
Cumulative inhibition of voltage-gated Na+ channel current (INa) caused by high-frequency depolarization plays a critical role in regulating electrical activity in excitable cells. As discussed in this review paper, exposure to certain small-molecule modulators can perturb INa during high-frequency stimulation, influencing the extent of cumulative inhibition and electrical excitability in excitable cells. Carbamazepine differentially suppressed transient or peak (INa(T)) and late (INa(L)) components of INa. Moreover, the cumulative inhibition of INa(T) during pulse-train stimulation at 40 Hz was enhanced by lacosamide. GV-58 was noted to exert stimulatory effect on INa(T) and INa(L). This stimulated INa was not countered by ω-conotoxin MVIID but was effectively reversed by ranolazine. GV-58′s exposure can slow down INa inactivation elicited during pulse-train stimulation. Lacosamide directly inhibited INa magnitude as well as promoted this cumulative inhibition of INa during pulse-train stimuli. Mirogabalin depressed INa magnitude as well as modulated frequency dependence of the current. Phenobarbital can directly modulate both the magnitude and frequency dependence of ionic currents, including INa. Previous investigations have shown that exposure to small-molecule modulators can perturb INa under conditions of high-frequency stimulation. This ionic mechanism plays a crucial role in modulating membrane excitability, hereby supporting the validity of these findings. Full article
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14 pages, 2153 KiB  
Article
The Effect of Insulin-like Growth Factor-1 on Protein Composition and DNA Content in Damaged Somatic Nerves
by Marina Parchaykina, Milena Simakova, Tatyana Kuzmenko, Anastasia Zavarykina, Elvira Revina, Elizaveta Sadovnikova, Igor Grunyushkin, Svetlana Kiryukhina and Victor Revin
Sci. Pharm. 2025, 93(3), 32; https://doi.org/10.3390/scipharm93030032 - 22 Jul 2025
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Abstract
This study investigated the changes in protein composition and DNA content in damaged somatic nerves when exposed to insulin-like growth factor-1 (IGF-1). Using electrophoretic protein separation in polyacrylamide gel (PAG) and spectrophotometry, the transection was shown to be accompanied by a significant decrease [...] Read more.
This study investigated the changes in protein composition and DNA content in damaged somatic nerves when exposed to insulin-like growth factor-1 (IGF-1). Using electrophoretic protein separation in polyacrylamide gel (PAG) and spectrophotometry, the transection was shown to be accompanied by a significant decrease in the quantitative content of total protein, certain protein fractions and DNA, both in the proximal and distal segments of the nerve conductor. Against the background of the intramuscular administration of IGF-1, intensive DNA synthesis and the protein composition stabilization of somatic nerves at the earlier post-traumatic stages were observed. By means of Raman scattering (RS-spectroscopy) and recording action potentials (APs), the enhanced recovery of the physicochemical condition of the nerve fiber membrane and its functional activity, indicating regeneration activation in the somatic nerves after damage, was revealed. IGF-1 was most likely to stimulate cytoskeleton protein synthesis through launching the mitogen-activated protein kinase signal pathway (MAPK/ERK), resulting in the increased expression of the genes related to the remyelination and functioning recovery of damaged nerve conductors. Full article
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28 pages, 1369 KiB  
Review
Expanding Horizons: Opportunities for Diclofenac Beyond Traditional Use—A Review
by Mykhailo Dronik and Maryna Stasevych
Sci. Pharm. 2025, 93(3), 31; https://doi.org/10.3390/scipharm93030031 - 16 Jul 2025
Viewed by 346
Abstract
This study systematically reviews the non-traditional pharmacological effects of diclofenac, a well-known nonsteroidal anti-inflammatory drug, to explore its potential for drug repositioning beyond its established analgesic and anti-inflammatory applications. A comprehensive literature search was conducted using the PubMed, Scopus and Web of [...] Read more.
This study systematically reviews the non-traditional pharmacological effects of diclofenac, a well-known nonsteroidal anti-inflammatory drug, to explore its potential for drug repositioning beyond its established analgesic and anti-inflammatory applications. A comprehensive literature search was conducted using the PubMed, Scopus and Web of Science databases, covering studies from 1981 to 2025. It was revealed that over 94% of records in Scopus and Web of Science are duplicated in PubMed, so the latter was used for the search in our study. After duplicate removal and independent screening, 89 from 1123 retrieved studies were selected for the search. The analysis revealed a broad spectrum of diclofenac’s non-traditional pharmacological activities, including neuroprotective, antiamyloid, anticancer, antiviral, immunomodulatory, antibacterial, antifungal, anticonvulsant, radioprotective, and antioxidant properties, primarily identified through preclinical In vitro and In vivo studies. These effects are mediated through diverse molecular pathways beyond cyclooxygenase inhibition, such as modulation of neurotransmitter release, apoptosis, and cellular proliferation. Diclofenac showed potential for repositioning in oncology, neurodegenerative disorders, infectious diseases, and immune-mediated conditions. Its hepatotoxicity and cardiovascular risks necessitate strategies like advanced drug formulations, dose optimization, and personalized medicine to enhance safety. Large-scale randomized clinical trials are essential to validate these findings and ensure safe therapeutic expansion. Full article
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24 pages, 3919 KiB  
Article
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
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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  
Case 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
Viewed by 367
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
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22 pages, 1889 KiB  
Article
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
Viewed by 322
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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