European Journal of Pharmaceutical Sciences最新文献

{"title":"Impact of protein adsorption during biopharmaceutical manufacture & storage","authors":"John D. Downey,&nbsp;Abina M. Crean,&nbsp;Katie B. Ryan","doi":"10.1016/j.ejps.2025.107071","DOIUrl":"10.1016/j.ejps.2025.107071","url":null,"abstract":"<div><div>Protein therapeutics contact multiple interfaces during formulation, filtration, fill-finish, and storage processes. Interactions at these interfaces can compromise the conformational and colloidal stability of therapeutic proteins through surface adsorption, potentially leading to aggregation and particle formation. Surface-induced conformational changes in protein higher-order structures, influenced by interfacial hydrophobicity and charge, are key drivers of these effects. The resulting loss of active protein and increased aggregation risk pose significant challenges to the efficacy and safety of the final biotherapeutic product. Thus, it is imperative to develop strategies that minimize protein-surface interactions that may compromise the protein's conformational and colloidal stability during manufacture and storage. This review focuses on current research related to the adsorption behaviour of biotherapeutics at interfaces encountered during fill-finish and storage. Furthermore, the review introduces the factors influencing protein adsorption and interfacial stability and current methodologies and advancements in mitigating interfacial adsorption, emphasizing rational formulation design strategies.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107071"},"PeriodicalIF":4.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647800","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":"Evaluating polymer influence on resuspendability of indomethacin suspensions produced by microfluidization","authors":"Mathias Dam Mønster Sørensen ,&nbsp;Fanjin Wang ,&nbsp;Maryam Parhizkar ,&nbsp;René Holm","doi":"10.1016/j.ejps.2025.107072","DOIUrl":"10.1016/j.ejps.2025.107072","url":null,"abstract":"<div><div>Long-acting injectables improve treatment outcomes for chronic diseases by reducing dosing frequency. Long-acting injectables may be formulated as nano- or microsuspensions produced by wet bead milling and homogenization often facing physical instability. This study investigates different stabilizers’ ability to prevent particle growth, caking and the influence on resuspendability. Eight different stabilizers; polysorbate 20 (PS20), polysorbate 80 (PS80), poloxamer 188 (P188), poloxamer 338 (P338), polyvinylpyrrolidone K17 (PVP K17), polyvinylpyrrolidone K30 (PVP K30), vitamin E-TPGS, and sodium lauryl sulphate (SLS) and one potential resuspending agent (polyethylene glycol 4000) was used to assess the stability and resuspendability of indomethacin suspensions. The stability and resuspendability was assessed during four weeks of storage at three different temperatures for all stabilizers at five different concentrations. PVP K30, PVP K17 and P338 yielded stable indomethacin suspensions with minor particle growth. Statistical and machine learning modelling identified stabilizer type as a critical factor influencing resuspendability. Increased storage temperature was found to negatively impact resuspendability, particularly in formulations containing polysorbates. Addition of the resuspending agent PEG4000 did not have significant impact on the resuspendability of vitamin E-TPGS and PS20 formulations while it had a negative effect on the resuspendability of formulations with PVP K30 and P338.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107072"},"PeriodicalIF":4.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647798","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":"Transport of statins by multidrug resistance-associated proteins 1 and 5","authors":"Suvi-Kukka Tuomi ,&nbsp;Feng Deng ,&nbsp;Mikko Neuvonen ,&nbsp;Mikko Niemi","doi":"10.1016/j.ejps.2025.107070","DOIUrl":"10.1016/j.ejps.2025.107070","url":null,"abstract":"<div><div>Statins are widely used in the treatment of hypercholesterolemia but also associated with muscle-related adverse effects. Multidrug resistance-associated protein (MRP) 1 and 5 are expressed in the skeletal muscle, where they may regulate intramuscular levels of their substrates. Here, we investigated the transport of various statins by MRP1 and MRP5 with the vesicular transport assay. Statin concentrations in the vesicles were determined with liquid chromatography tandem mass spectrometry. At 6 µM statin concentration, MRP1 transported both 3R,5S-fluvastatin and 3S,5R-fluvastatin with uptake ratios of 2.6 and 2.0. MRP5 transported 3R,5S-fluvastatin, 3S,5R-fluvastatin, and 10 µM pitavastatin with uptake ratios of 2.9, 3.7, and 2.6, respectively. Atorvastatin was only a weak substrate of MRP5 with an uptake ratio of 1.6 and was therefore not investigated further. In concentration-dependent transport experiments, racemic fluvastatin was transported by MRP1 and MRP5 with apparent affinities (K_m) of 225 µM and 23 µM. Pitavastatin was transported by MRP5 with a K_m value of 433 µM. <em>In vitro</em> clearance (CL<em>_{in vitro}</em>) of fluvastatin was 0.36 µl/min/mg for MRP1, while MRP5 exhibited a CL<em>_{in vitro}</em> value of 1.2 µl/min/mg for fluvastatin and 0.21 µl/min/mg for pitavastatin. Pravastatin, rosuvastatin, and simvastatin acid were not transported by MRP1 or MRP5. Atorvastatin and pitavastatin were not transported by MRP1. These data indicate that MRP1 transports fluvastatin, while MRP5 transports both fluvastatin and pitavastatin. Because MRP1 and MRP5 are expressed in the skeletal muscle, they may reduce myocyte exposure to fluvastatin and pitavastatin and protect from muscle toxicity.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107070"},"PeriodicalIF":4.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633976","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":"Hierarchical clustering of therapeutic proteins based on agitation-induced aggregation propensity and its relation to physicochemical parameters","authors":"Rio Okada ,&nbsp;Kosei Shibata ,&nbsp;Risa Shibuya ,&nbsp;Tetsuo Torisu ,&nbsp;Susumu Uchiyama","doi":"10.1016/j.ejps.2025.107060","DOIUrl":"10.1016/j.ejps.2025.107060","url":null,"abstract":"<div><div>Physical stresses such as agitation induce protein aggregation, which causes adverse effects on the immune system of patients, leading to challenges in drug development. Aggregation induced by physical stresses can be minimized by formulation optimization. In this study, 120 combinations of 10 therapeutic proteins and 12 different formulations (4 pH conditions and 3 salt concentrations) were prepared. Subsequently, the agitation-induced aggregation propensity of each protein was investigated by evaluating its monomer recovery (%) using size exclusion chromatography. Hierarchical clustering was applied to categorize each protein according to its aggregation propensity, resulting in two groups of proteins: group A and B. The aggregation propensity of proteins in group A was insensitive to changes in formulation conditions because conformational, colloidal, and interfacial stabilities were minimally affected by changes in the pH and salt concentration and a compensation mechanism existed between conformational and colloidal stabilities. Thus, proteins in group A can be formulated with a relatively high degree of freedom. In contrast, the aggregation propensity of proteins in group B was sensitive to changes in formulation conditions. Multiple regression analysis of the physicochemical parameters and monomer recovery of proteins in group B clarified that changes in conformational stability in response to changes in formulations primarily contributed to the sensitivity of the monomer recovery to changes in formulation conditions. For all antibodies, there was a positive correlation between the monomer recovery after agitation and that after quiescent storage at 40 °C for 1 month, suggesting that a stable formulation can be obtained without the quiescent testing. Therefore, a proposed formulation optimization strategy based on the agitation-induced monomer recovery can improve the efficiency of formulating selected therapeutic proteins. This strategic approach is expected to accelerate the development of therapeutic proteins while reflecting the importance of aggregation factors and quiescent stability in the optimization of therapeutic protein formulations.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"208 ","pages":"Article 107060"},"PeriodicalIF":4.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143610232","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":"Direct comparison of single peak and gradient chromatographic methods for routine analysis of surfactants in biopharmaceuticals","authors":"Maksymilian M. Zegota ,&nbsp;Juliane Achenbach ,&nbsp;Georg Schuster ,&nbsp;Christian Schöneich ,&nbsp;Tim Menzen ,&nbsp;Andrea Hawe","doi":"10.1016/j.ejps.2025.107065","DOIUrl":"10.1016/j.ejps.2025.107065","url":null,"abstract":"<div><div>The non-ionic surfactants polysorbate 20, polysorbate 80 and poloxamer 188 are prone to degradation, which necessitates their monitoring as part of the analytical strategy for surfactant- containing biopharmaceuticals. In this study, we discuss the challenges of analyzing partially degraded surfactant samples in the context of the most common quantification method – online solid-phase extraction using a mixed-mode column with analyte elution as a single peak. Additionally, we compare this single peak approach with gradient methods for surfactant quantification. To facilitate this comparison, we developed a simple gradient approach that allows for the rapid profiling of both polysorbates in 5.5 minutes and poloxamer 188 in 11 minutes, using liquid chromatography (LC) coupled with charged aerosol detection (CAD) or mass spectrometry (MS). We also included polyethylene glycol 15 hydroxystearate (HS15) as a possible alternative to the established surfactants. The gradient approach is a stability-indicating method that can detect compositional changes due to common degradation pathways, such as those induced by hydrolytic or oxidative stress, based on changes in the elution profile. The sensitivity of the single peak approach to degradation varies depending on the root cause. In conclusion, we present a workflow in which one chromatographic column employing fast gradients enables effective separation of the main surfactant components, facilitating both qualitative and quantitative analysis, as well as root cause analysis in case of observed degradation.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107065"},"PeriodicalIF":4.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630277","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":"DprE1 inhibitors: An insight into the recent developments and synthetic approaches","authors":"Mai I. Shahin ,&nbsp;Mai A. Elyamani ,&nbsp;Ahmed E. Elsawi ,&nbsp;Ahmed T. Negmeldin ,&nbsp;Shahenda Naguib ,&nbsp;Heba Safwat ,&nbsp;Hatem A. Abdel-Aziz ,&nbsp;Wagdy M. Eldehna","doi":"10.1016/j.ejps.2025.107062","DOIUrl":"10.1016/j.ejps.2025.107062","url":null,"abstract":"<div><div>In the current medical era, the proliferation and dissemination of drug-resistant strains of <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) continue to pose a significant worldwide health hazard, necessitating the development of new and innovative medications to combat tuberculosis. Decaprenylphosphoryl-β-D-ribose 2′-epimerase (DprE1) is a crucial enzyme for cell wall synthesis in <em>Mtb</em>. Its importance is due to its eminent contribution in forming lipoarabinomannan and arabinogalactan, key components of the mycobacterial cell wall. The emergence of the DprE1 enzyme as a druggable target was based on inhibitors discovered in high-throughput screening. Since then, inhibitors with different types of chemical scaffolds have been reported for their activity against it. DprE1 inhibitors can be categorized according to the formation of a covalent or non-covalent bond in the enzyme's active site, causing a loss of its catalytic activity, leading to <em>Mtb</em>'s demise. Herein, we describe diverse DprE1 inhibitors that have had anti-tubercular activity reported over the past fifteen years and till the present time.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107062"},"PeriodicalIF":4.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614075","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":"Enhancing Martini 3 for protein self-interaction simulations","authors":"Jonas Binder ,&nbsp;Matja Zalar ,&nbsp;Martin Huelsmeyer ,&nbsp;Michael Siedler ,&nbsp;Robin Curtis ,&nbsp;Wolfgang Friess","doi":"10.1016/j.ejps.2025.107068","DOIUrl":"10.1016/j.ejps.2025.107068","url":null,"abstract":"<div><div>Coarse-grained molecular dynamics simulations are highly valuable for studying protein-protein interactions. Unfortunately, commonly used force fields often overestimate these interactions. Here, we investigate the performance of the Martini 3 force field in predicting the self-interaction behavior of lysozyme and subtilisin using Metadynamics. The original Martini 3, despite improvements over its predecessor, overestimates interaction strength. Through reparameterization of bead interactions, we achieve good agreement with experimental data of the second virial coefficient and the diffusion coefficient. The new, refined force field enables more accurate CG-MD simulations, with potential applications in understanding and prediction of protein stability, aggregation tendencies, and solubility, with the possibility to aid in the development of protein-based drugs.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107068"},"PeriodicalIF":4.3,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614076","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":"Enhancing drug release from PEG-PLGA implants: The role of Hydrophilic Dexamethasone Phosphate in modulating release kinetics and degradation behavior","authors":"Eric Lehner ,&nbsp;Marie-Luise Trutschel ,&nbsp;Matthias Menzel ,&nbsp;Jonas Jacobs ,&nbsp;Julian Kunert ,&nbsp;Jonas Scheffler ,&nbsp;Wolfgang H. Binder ,&nbsp;Christian E.H. Schmelzer ,&nbsp;Stefan K. Plontke ,&nbsp;Arne Liebau ,&nbsp;Karsten Mäder","doi":"10.1016/j.ejps.2025.107067","DOIUrl":"10.1016/j.ejps.2025.107067","url":null,"abstract":"<div><div>Poly(lactic-co-glycolic acid) (PLGA) is a prominent biodegradable polymer used in biomedical applications, including drug delivery systems (DDS) and tissue engineering. PLGA's ability to control drug release is often hindered by nonlinear release profiles and slow initial drug release for hydrophobic drugs. This study investigates the incorporation of dexamethasone phosphate (DEXP) into polyethylene glycol–poly(lactic-co-glycolic acid) (PEG-PLGA) implants to enhance the initial release rate of dexamethasone (DEX). Implants were fabricated via hot-melt extrusion with varying DEX to DEXP ratios. X-ray diffraction (XRD) analysis confirmed that DEX remained crystalline in all formulations, whereas DEXP's crystallinity was detectable only in higher concentrations. Energy-dispersive X-ray spectroscopy (EDX) provided insights into the distribution of DEX and DEXP within the polymer matrix. Drug release studies revealed that PEG-PLGA implants accelerated initial drug release with increasing quantity of DEXP, though it also led to a shorter overall release duration. Despite these improvements, all implants exhibited a biphasic release profile. DEXP also influenced the characteristics of the polymer matrix, evidenced by increased swelling, water absorption, and mass loss. ¹H NMR analysis revealed a faster decrease in glycolic acid monomers in DEXP-containing implants. These findings demonstrate that DEXP enhances early drug release of DEX-loaded PEG-PLGA implants prepared by hot-melt extrusion. However, balancing initial and sustained release profiles remains challenging.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107067"},"PeriodicalIF":4.3,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604336","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":"Pharmacological countermeasures for long-duration space missions: addressing cardiovascular challenges and advancing space-adapted healthcare","authors":"Audrey Derobertmasure ,&nbsp;Li Shean Toh ,&nbsp;Virginia E Wotring ,&nbsp;Philip M Williams ,&nbsp;Lucia Morbidelli ,&nbsp;Julia C Stingl ,&nbsp;Mathieu Vinken ,&nbsp;Raghda Ramadan ,&nbsp;Stephanie Chhun ,&nbsp;Pierre Boutouyrie","doi":"10.1016/j.ejps.2025.107063","DOIUrl":"10.1016/j.ejps.2025.107063","url":null,"abstract":"<div><div>Future long-duration crewed space missions beyond Low Earth Orbit (LEO) will bring new healthcare challenges for astronauts for which pharmacological countermeasures (pharmacological countermeasures) are crucial. This paper highlights current pharmacological countermeasures challenges described in the ESA SciSpacE Roadmap, with a focus on the cardiovascular system as a model to demonstrate the potential implication of the challenges and recommendations. New pharmacological approaches and procedures need to be adapted to spaceflight (spaceflight) conditions, including ethical and reglementary considerations. Potential strategies include combining pharmacological biomarkers such as pharmacogenomics with therapeutic drug monitoring, advancing microsampling techniques, and implementing a pharmacovigilance system to gain deep insights into pharmacokinetics/pharmacodynamics (PK/PD) spaceflight alteration on drug exposure. Emerging therapeutic approaches (such as long-term regimens) or manufacturing drugs in the space environment, can address specific issues related to drug storage and stability.</div><div>The integration of biobanks and innovative technologies like organoids and organ-on-a-chip, artificial intelligence (AI), including machine learning will further enhance PK modelling leading to personalized treatments. These innovative pharmaceutical tools will also enable reciprocal game-changing healthcare developments to be made on Earth as well as in space and are essential to ensure space explorers receive safe effective pharmaceutical care.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107063"},"PeriodicalIF":4.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596329","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":"Light-mediated activation/deactivation control and in vitro ADME-Tox profiling of a donepezil-like Dual AChE/MAO-B Inhibitor","authors":"Federica Poggialini ,&nbsp;Paolo Governa ,&nbsp;Chiara Vagaggini ,&nbsp;Samuele Maramai ,&nbsp;Stefania Lamponi ,&nbsp;Claudia Mugnaini ,&nbsp;Antonella Brizzi ,&nbsp;Rosa Purgatorio ,&nbsp;Modesto de Candia ,&nbsp;Marco Catto ,&nbsp;Elena Dreassi ,&nbsp;Fabrizio Manetti ,&nbsp;Federico Corelli ,&nbsp;Cosimo Damiano Altomare ,&nbsp;Andrea Cappelli ,&nbsp;Marco Paolino","doi":"10.1016/j.ejps.2025.107066","DOIUrl":"10.1016/j.ejps.2025.107066","url":null,"abstract":"<div><div>The possibility to control the effects of drugs in time and space represents an ideal condition for developing safer and more personalized therapies against different disorders. In this context, photopharmacology has paved the way for the use of light in the modulation of drugs activity. Our interest is directed to photo-switchable molecules, capable of interconverting between two different isoforms upon light irradiation. We recently reported <strong>1</strong>, a donepezil-like compound based on 2-benzylidenindan-1-one structure, as a dual AChE and MAO-B inhibitor, which can be converted into the <em>E</em>- (active form) and <em>Z</em>- (about tenfold less active form) diastereoisomers by irradiating with UV–vis light. Aiming at identifying compounds with remarkable activity in physiological conditions, we herein report a fine characterization of <strong>1</strong> in PBS solutions. First, we evaluated its ability to act as a photoswitch comparing PBS solution with organic solvents (e.g. methanol), demonstrating that a wavelength in the UV range (330 nm) can convert the <em>E-</em> into the <em>Z-</em>diastereoisomer, while the use of a visible light (400 nm) allows the interconversion from <em>Z</em> to <em>E</em> in both media. Along with its photoinducible behavior, we investigated the passive diffusion across cellular membrane with PAMPA experiments, plasma and microsomal stability, and binding to plasma proteins. Interestingly, the results of such studies suggested that <strong>1</strong> could persist in the blood circulation for a long time, which is desirable for application in photopharmacological therapies. Cytotoxicity studies highlighted the potential of our prototypic compound as a lead photodrug against neurodegenerative disorders, deserving to advance in molecular optimization studies and further in vitro and in vivo characterization.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107066"},"PeriodicalIF":4.3,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596613","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}