European Journal of Pharmaceutical Sciences最新文献

{"title":"Optimized PLGA encapsulated SA-2 nanosuspension exhibits sustained intraocular pressure reduction in the mouse microbead occlusion model of ocular hypertension","authors":"Charles E. Amankwa ,&nbsp;Biddut DebNath ,&nbsp;Jennifer H. Pham ,&nbsp;Gretchen A. Johnson ,&nbsp;Wei Zhang ,&nbsp;Amalendu Ranjan ,&nbsp;Dorota L. Stankowska ,&nbsp;Suchismita Acharya","doi":"10.1016/j.ejps.2025.107016","DOIUrl":"10.1016/j.ejps.2025.107016","url":null,"abstract":"<div><div>Elevated intraocular pressure (IOP) is implicated in the structural and functional damage to the retinal ganglion cells (RGCs) in primary open-angle glaucoma (POAG). Topical IOP lowering agents provide short-term relief, necessitating frequent dosing. Moreover, non-adherence to frequent eyedrops administration contributes significantly to visual field loss and worsens the disease outcome. We optimized the poly (lactic-co-glycolic acid) (PLGA) nanoparticles encapsulation of hybrid antioxidant-nitric oxide donor SA-2 (<strong>SA-2NP</strong>), investigated its bioavailability, duration of IOP lowering efficacy, and effects on retinal function in the microbead model of ocular hypertension (OHT).</div><div>SA-2 was bioavailable in the anterior and posterior segments after 1, 8, and 24 h post-single topical eyedrop administration. SA-2NP significantly lowered IOP (∼25–34%) and preserved the RGC function after weekly eyedrop administration for 3 weeks in C57BL/6J mice. In conclusion, the optimized SA-2NP formulation demonstrated optimal bioavailability, ocular safety, and prolonged IOP-lowering efficacy in the mouse microbead occlusion model of OHT.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"206 ","pages":"Article 107016"},"PeriodicalIF":4.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamins as excipients in pharmaceutical products","authors":"Anne-Cécile V. Bayne ,&nbsp;Jenni Pessi ,&nbsp;Julia K. Bird ,&nbsp;René T. Stemmler ,&nbsp;Margarita Frerichs ,&nbsp;Ahmed Besheer","doi":"10.1016/j.ejps.2025.107020","DOIUrl":"10.1016/j.ejps.2025.107020","url":null,"abstract":"<div><div>Excipients are ingredients in pharmaceutical products other than the active ingredient, added to facilitate manufacturing, enhance stability or modulate release and bioavailability. Vitamins are diverse molecules essential for human nutrition that also can fulfil excipient functions. This review focuses on vitamins used as excipients and provides an overview of the functions of vitamins in various pharmaceutical formulations. A thorough search was conducted to understand the current use of vitamins in marketed drug products, concluding that many vitamins are already used as functional excipients. Vitamins are used widely in different dosage forms, including oral, parenteral, and topical formulations, and alongside a broad range of active pharmaceutical ingredients, biologics, and small molecules from different biopharmaceutical classification system classes. Many examples of the use of vitamins to improve the performance of the pharmaceutical formulation in which they are included are presented and the mode of action of vitamins as excipients in the product is reviewed. Furthermore, the potential for future uses of vitamins in pharmaceutical products is highlighted. Lastly, considerations for the use of vitamins as excipients in drug products as well as the regulatory framework are discussed.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"206 ","pages":"Article 107020"},"PeriodicalIF":4.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transporter expressions as part of required scaling factor to support in vitro in vivo extrapolation for blood-brain barrier drug permeability","authors":"Zubida M. Al-Majdoub ,&nbsp;Jonathan Cheong ,&nbsp;Kunihiko Mizuno ,&nbsp;Janita Hogan ,&nbsp;Tom De Bruyn ,&nbsp;Anne Kanta ,&nbsp;Jingjing Guo ,&nbsp;Cornelis E.C.A. Hop ,&nbsp;Mike Zientek ,&nbsp;Aleksandra Galetin ,&nbsp;Kayode Ogungbenro ,&nbsp;Amin Rostami-Hodjegan ,&nbsp;Jill Barber","doi":"10.1016/j.ejps.2025.107022","DOIUrl":"10.1016/j.ejps.2025.107022","url":null,"abstract":"<div><div>Access of drugs to the central nervous system is limited by the blood–brain barrier, and this in turn affects drug efficacy/toxicity. To date, most drug discovery optimization paradigms have relied heavily on in vitro transporter assays and preclinical species pharmacokinetic evaluation to provide a qualitative assessment of human brain penetration. Because of the lack of human brain pharmacokinetic data, mechanistic models for preclinical species, combined with in vitro and in silico data, are useful for translation to human. These models require transporter expression data to be measured in both in vitro and in vivo systems. The purpose of this work was to quantify transporter expression and generate scaling factors (SFs) to enable in vitro in vivo extrapolation (IVIVE) of transporter-mediated processes and to support the development of PBPK model of the brain in rats. SF represents the ratio of abundance of the relevant transporter in the tissue relative to transporter expressing cells. Using quantitative proteomics with QconCAT technology, the expression of human and rat P-gp (ABCB1/Abcb1) and BCRP/Bcrp (ABCG2/Abcg2) was measured in rat brain microvessels, mock and transfected cell lines including, Madin-Darby Canine Kidney I (MDCK I), Madin-Darby Canine Kidney II (MDCK II) and Porcine Kidney epithelial cells (LLC-PK1). P-gp expression ranged from 32 to 71 pmol/mg in rat brain microvessels, exceeding literature values of 14.1–25.2 pmol/mg protein. Conversely, Bcrp expression ranged between 0.02–0.27 pmol/mg protein lower than the literature range (2–6.2 pmol/mg protein). P-gp expression in MDCK I and LLC-PK1 cells transfected with rat Mdr1a was similar (within 1.5-fold) as was human P-gp expression in MDR1 transfected LLC-PK1 and MDCK II cells. The generated SFs were 34.4 and 50.4 for brain P-gp (depending on the cell line used) and 0.53 for brain Bcrp. Endogenous P-gp transporter was detected in MDCK II cell lines when protein expression was measured using a surrogate peptide that was shared across species. The current work provides a framework for proteomics-informed translation of in vitro P-gp and BCRP-related kinetics of drugs and supports the development of PBPK models to predict drug disposition in the brain.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107022"},"PeriodicalIF":4.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of community pharmacies on equity in access to professional rapid antigen testing for SARS-CoV-2 in Portugal","authors":"José Guerreiro ,&nbsp;Sónia Romano ,&nbsp;Inês Teixeira ,&nbsp;Klára Dimitrovová ,&nbsp;Rúben Pereira ,&nbsp;António Teixeira Rodrigues ,&nbsp;Ema Paulino","doi":"10.1016/j.ejps.2025.107019","DOIUrl":"10.1016/j.ejps.2025.107019","url":null,"abstract":"<div><h3>Introduction</h3><div>Amid the COVID-19 pandemic, various public health measures were adopted to reduce the transmission risk, including the full reimbursement of SARS-CoV-2 professional rapid antigen detection tests (Ag-RDT) conducted in clinical pathology laboratories, community pharmacies (CPs), and other authorized entities. This study aimed to assess the impact of integrating CPs into the Portuguese National Health Service (NHS) testing strategy on the capacity of professional Ag-RDT delivery, and to compare the equity in testing access with and without CPs participation.</div></div><div><h3>Methods</h3><div>This analytical cross-sectional study assessed the impact of adding CPs into the testing strategy based on two main outcomes by municipality: (i) average distance (in Kilometres) of the population to the nearest Ag-RDT site; and (ii) the average number of weekly hours available to testing per 1,000 inhabitants, as of January 31, 2022. Two scenarios were considered: with and without CPs. Access inequalities were evaluated using Lorenz curves and Gini coefficients. A subgroup inequality analysis was conducted based on three socio-demographic indicators: population density, aging index, and per capita purchasing power index.</div></div><div><h3>Results</h3><div>A total of 1,369 (65.1 %) pharmacies and 735 (34.9 %) laboratories and other entities provided free Ag-RDT to the population. The average distance to the nearest Ag-RDT location was 3.7 km, which decreased to 1.8 km with the inclusion of CPs. Overall, there were 11.5 weekly hours per 1,000 inhabitants available for testing with CPs, compared to 2.1 h without CPs (<em>p</em> &lt; 0.0001). The Gini coefficient for distance distribution decreased from 0.50 to 0.42 with CPs inclusion (-16.8 %). For the distribution of weekly hours, the Gini coefficient decreased from 0.42 to 0.26 (-38.6 %). The reduction was higher in municipalities with lower population density (-43.3 %), higher aging index (-51.3 %), and lower per capita purchasing power index (-54.6 %).</div></div><div><h3>Conclusions</h3><div>Pharmacies play a crucial role in mitigating geographical and socioeconomic inequalities in healthcare access. Without CPs, the provision of Ag-RDT services would result in significant territorial gaps, exacerbating disparities among already vulnerable population groups.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"206 ","pages":"Article 107019"},"PeriodicalIF":4.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation of dried nanoemulsion formulation by electrospinning","authors":"Josip Ljubica ,&nbsp;Črt Dragar ,&nbsp;Tanja Potrč ,&nbsp;Mirjam Gosenca Matjaž ,&nbsp;Mirjana Gašperlin ,&nbsp;Laura Nižić Nodilo ,&nbsp;Ivan Pepić ,&nbsp;Jasmina Lovrić ,&nbsp;Petra Kocbek","doi":"10.1016/j.ejps.2025.107015","DOIUrl":"10.1016/j.ejps.2025.107015","url":null,"abstract":"<div><div>Dry eye disease is a multifactorial condition characterized by a loss of homeostasis of the tear film. Among the various treatment approaches, the application of ophthalmic oil-in-water nanoemulsions with incorporated anti-inflammatory drugs represents one of the most advanced approaches. However, the liquid nature of nanoemulsions limits their retention time at the ocular surface. Transforming the nanoemulsions into a dry form that would disperse rapidly in the tear fluid would improve the retention of the drug at the ocular surface. The aim of this study was to investigate electrospinning as a method for the preparation of a solid eye preparation based on nanoemulsion loaded with the anti-inflammatory drug loteprednol etabonate. Four nanoemulsions differing in oil-to-surfactant ratios were incorporated in hydrophilic nanofibers based on polyethylene oxide, poloxamer 188, and Soluplus®. The dried nanoemulsions in the form of nanofibers dispersed readily on contact with aqueous medium, resulting in a dispersion of nanometre-sized droplets with average size comparable to the average droplet size of the initial nanoemulsions. A rheological study revealed the predominant elastic behavior of the dispersed nanofibers, which indicates the formation of a weak gel after the dispersion of the dried nanoemulsion in tear fluid at the ocular surface. The biocompatibility of the dried nanoemulsions in the form of nanofibers after a single and multiple-dose application was confirmed using the 3D HCE-T model of the stratified epithelium of the human cornea, suggesting that this innovative solid eye preparation could represent a new approach to the treatment of dry eye disease.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"206 ","pages":"Article 107015"},"PeriodicalIF":4.3,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilizing effect of HP-β-CD on infliximab in liquid formulations and a solid formulation produced by electrospinning","authors":"Fanni Angéla Geyer ,&nbsp;Júlia Domján ,&nbsp;Tibor Viktor Szalai ,&nbsp;Zsolt Rapi ,&nbsp;Zoltán Varga ,&nbsp;György Marosi ,&nbsp;Zsombor K. Nagy ,&nbsp;Edit Hirsch","doi":"10.1016/j.ejps.2025.107014","DOIUrl":"10.1016/j.ejps.2025.107014","url":null,"abstract":"<div><div>The development of stable biopharmaceutical formulations, such as monoclonal antibodies, poses a great challenge in the pharmaceutical industry. This study investigated the stabilizing effect of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in liquid and solid formulations of infliximab during processing and storage. The solid formulation was produced by a scaled-up high-speed electrospinning method, resulting in a product suitable for reconstitution with excellent dissolution properties. Liquid formulations contained exclusively HP-β-CD as a stabilizing excipient at different concentrations. Both types of formulations were stored under various conditions for up to 6 months, and infliximab stability was compared based on monomer recovery and the analysis of fragments and aggregates. The solid formulation stored at low (-18 °C, 4 °C) temperatures and lower humidity conditions show the most promising results. Moreover, the monomer loss was less than 10 % even at room temperature storage after 2 months, indicating a potentially good temperature tolerance. Increasing HP-β-CD content in liquid formulations significantly improved the long-term stability of infliximab while enhancing protection against mechanical stress. Furthermore, to better understand the stabilizing mechanism of HP-β-CD on infliximab, the molecular interactions were investigated by bio-layer interferometry and isothermal titration calorimetry methods. The experiments proved that the presence of HP-β-CD decreased infliximab self-interaction, correlating with the aggregation-suppressing effect of HP-β-CD observed during the stress- and long-term stability studies. The results demonstrate the potential of HP-β-CD as a stabilizing excipient in liquid and solid formulations of infliximab.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"206 ","pages":"Article 107014"},"PeriodicalIF":4.3,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining in vitro, in vivo, and in silico approaches to evaluate the effect of serotonergic-based topical therapies on mild to moderate psoriasis","authors":"Ana M. Martins ,&nbsp;Lídia Gonçalves ,&nbsp;Sandra Simões ,&nbsp;Patrícia A. Serra ,&nbsp;Rita C. Guedes ,&nbsp;Helena Ribeiro ,&nbsp;Joana Marto","doi":"10.1016/j.ejps.2025.107013","DOIUrl":"10.1016/j.ejps.2025.107013","url":null,"abstract":"<div><div>Psoriasis, a chronic inflammatory skin disease, poses a significant burden on patients’ quality of life and healthcare systems. While mild-to-moderate cases are treated topically, usually combined with phototherapy, severe cases require systemic treatment with immunosuppressants, retinoids or biologics. However, all available treatments have drawbacks in terms of efficiency and side effects. Drawing from studies linking depression treatment to psoriasis improvement, we investigated whether topical formulations of selective serotonin reuptake inhibitors (SSRIs) could offer a viable therapy for psoriasis. Five SSRIs (sertraline, fluoxetine, paroxetine, escitalopram, fluvoxamine) were evaluated for their <em>in vitro</em> cytotoxicity, in human keratinocytes and THP-1 monocytes. Their anti-inflammatory action was tested using cell differentiation assays and immunoassays of pro-inflammatory cytokines in THP-1 monocytes. The results obtained with sertraline, escitalopram, and fluvoxamine suggested further evaluation <em>in vivo</em>. Anti-inflammatory effects were evaluated by skin parameter monitoring and histopathology, in an imiquimod-induced psoriasis-like inflammation mice model, and the best results were obtained for fluvoxamine<em>.</em> These findings were further supported by <em>in silico</em> molecular docking studies of the structural interaction between the serotonergic receptors and the drugs. Future research will focus on developing and characterizing of topical fluvoxamine formulations, like emulsions and penetration-enhancer vesicles, which offer advantages over the gels used herein.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"206 ","pages":"Article 107013"},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of vial quality on interactions, particle formation, container closure integrity, and gas permeability for frozen drug product storage","authors":"Daniela Henle ,&nbsp;Lukas Muehlfeld ,&nbsp;Daniel Molnar ,&nbsp;Patrick Garidel ,&nbsp;Wolfgang Friess","doi":"10.1016/j.ejps.2025.107011","DOIUrl":"10.1016/j.ejps.2025.107011","url":null,"abstract":"<div><div>The frozen storage of biopharmaceuticals brings new challenges to the primary packaging material. Due to an increasing demand and the downsides of standard type I glass vials, such as vial breakage, novel vial types for special applications of parenteral drug products have been introduced to the market in the past years. Mechanical stresses due to dimensional changes experienced during freezing and thawing could change the material properties, hence affecting the interaction with the drug product stored in the vial or functionality such as overall integrity. Therefore, we studied the suitability of different vial qualities related to the thermally induced mechanical stresses experienced during frozen drug product preparation and storage. First, the possible failure modes for each vial type were identified. The interaction between vial surface and drug product were investigated considering surface hydrophobicity, surface free energy and surface roughness as well as microscopically visible changes analyzed by confocal laser scanning microscopy. Differences in surface hydrophobicity, roughness and surface free energy between the vial types did not impact the performance upon freeze-thaw stress and did not change with the stress. Screening the vial content for particles originating from the container using light and electron scanning microscopy combined with energy-dispersive X-ray spectroscopy showed only rare cases of particles in coated glass vials. Under extreme stress conditions, including a drop-test in the frozen state, a low number of particles was also detected in coated polymer vials. No quality issues regarding the functionality were observed upon container closure integrity testing, while the oxygen permeability was slightly increased for uncoated and especially coated polymer vials. Overall, the results show that several vial types are appropriate for the frozen storage of drug products and selection should be based on the formulation and other product requirements.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"206 ","pages":"Article 107011"},"PeriodicalIF":4.3,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heparan sulfate proteoglycan affinity of adeno-associated virus vectors: Implications for retinal gene delivery","authors":"Dimitri Romanovsky ,&nbsp;Hanna Scherk ,&nbsp;Bastian Föhr,&nbsp;Sabrina Babutzka,&nbsp;Jacqueline Bogedein,&nbsp;Yi Lu,&nbsp;Alice Reschigna,&nbsp;Stylianos Michalakis","doi":"10.1016/j.ejps.2025.107012","DOIUrl":"10.1016/j.ejps.2025.107012","url":null,"abstract":"<div><div>Adeno-associated virus (AAV)-based vectors have emerged as an effective and widely used technology for somatic gene therapy approaches, including those targeting the retina. A major advantage of the AAV technology is the availability of a large number of serotypes that have either been isolated from nature or produced in the laboratory. These serotypes have different properties in terms of sensitivity to neutralizing antibodies, cellular transduction profile and efficiency. The infectivity of AAV vectors depends on the affinity to certain molecules on the cell surface, in particular to cellular glycosaminoglycans (GAGs) such as heparan sulfate proteoglycans (HSPGs). Here, we tested how altering HSPG affinity in AAV vectors affects cellular tropism and transduction efficiency. The previously developed AAV2.GL variant was used as a starting variant to alter or disrupt HSPG affinity. The HSPG-independent AAV9 serotype was used to introduce different HSPG-binding sites. As an indicator of HSPG affinity, we measured the binding strength of the vector variant on a heparin chromatography column. We show that modification of capsid-exposed residues has a strong impact on HSPG affinity, cellular tropism and transduction efficiency in HeLa cells and in vivo in mouse retina. Our study shows that key properties of AAV vectors can be tailored in different directions and used to improve tropism and efficiency.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"206 ","pages":"Article 107012"},"PeriodicalIF":4.3,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro study of the pro-apoptotic mechanism of amino acid Schiff base copper complexes on anaplastic thyroid cancer","authors":"Peiran Zhao ,&nbsp;Xinyan Zhang ,&nbsp;Jianfang Dong ,&nbsp;Lianzhi Li ,&nbsp;Xiao Meng ,&nbsp;Lei Gao","doi":"10.1016/j.ejps.2025.107005","DOIUrl":"10.1016/j.ejps.2025.107005","url":null,"abstract":"<div><div>In the endocrine system, anaplastic thyroid cancer (ATC) is extremely aggressive since it inhibits the majority of medications and treatments. Therefore, there is an immediate demand to identify new treatment approaches or drugs to deal with ATC. Recently, amino acid Schiff base copper complexes have received great attention due to their excellent anti-tumor activity. In this research, three copper(II) complexes, [Cu(<em>o</em>-van-D-Trp)(phen)]<strong>(1)</strong>, [Cu(<em>o</em>-van-D-Trp)(bipy)]<strong>(2)</strong>, [Cu(naph-D-Trp)(bipy)]<strong>(3)</strong>, [D-Trp = D-tryptophan; o-van = <em>o</em>-vanillin; naph = 2‑hydroxy-1- naphthaldehyde; phen = 1,10-phenanthroline; bipy = 2,2-biprydine], have been synthesized and investigated as potential anticancer agents. The crystal structure data of the complexes demonstrate that the central copper (II) atom forms a twisted polyhedral environment with nitrogen and oxygen atoms. The MTT results demonstrated that three complexes exhibited superior cytotoxicity against five cell lines of thyroid cancer (Cal-62 cells, ARO cells, KHM-5 m cells, BHP10–3 cells and K1 cells), especially complex <strong>1</strong> with the IC₅₀ values of 0.59±0.05 μM, 2.36±0.47 μM, 1.10±0.87 μM, 0.75±0.09 μM, 1.72±0.06 μM, when cisplatin was used as a control. Research on antitumor mechanisms has demonstrated that complex <strong>1</strong> can significantly reduce the mitochondrial membrane potential, raise autophagy, and produce reactive oxygen species (ROS) in ARO cells in a dose-dependent manner. RNA sequencing study reveals that complex <strong>1</strong> may cause apoptosis in ARO cells and exhibit anticancer efficacy <em>in vitro</em> through ROS-mediated downregulation of Akt and p38 MAPK activation.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"206 ","pages":"Article 107005"},"PeriodicalIF":4.3,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}