Scientia Pharmaceutica

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

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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

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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

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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

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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

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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

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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

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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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Sci. Pharm., Volume 93, Issue 2 (June 2025) – 7 articles

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