European Journal of Pharmaceutical Sciences最新文献

{"title":"Comparative evaluation of a novel card-based spacer (MDI PLUS®) versus traditional aerochamber plus®: In-vivo and ex-vivo bioavailability study","authors":"Hasnaa Osama ,&nbsp;Wesam G. Ammari ,&nbsp;Ahmed H.M. Sobh ,&nbsp;Marwa Mohsen ,&nbsp;Marina Emad Boules ,&nbsp;Basma M.E. Mohamed ,&nbsp;Omar Ahmed Sayed ,&nbsp;Mohamed E.A. Abdelrahim ,&nbsp;Haitham Saeed","doi":"10.1016/j.ejps.2025.107215","DOIUrl":"10.1016/j.ejps.2025.107215","url":null,"abstract":"<div><h3>Background</h3><div>Effective aerosol delivery via pressurized metered dose inhalers (pMDIs) is often compromised by poor actuation–inhalation coordination. Spacer devices are commonly used to improve lung deposition. This study aimed to compare the lung and systemic bioavailability of salbutamol delivered via pMDI alone, with a traditional AeroChamber Plus® spacer, and with a novel disposable MDI Plus® carton spacer.</div></div><div><h3>Methods</h3><div>In a randomized, three-period crossover study, 20 healthy adults received 5 puffs (100 µg/puff) of salbutamol via each inhalation setup. Urine samples were collected 30 min post-inhalation (for lung bioavailability) and over 24 h (for systemic absorption). An ex-vivo setup using inhalation filters was also employed to quantify total delivered dose.</div></div><div><h3>Results</h3><div>The ex-vivo mean ± SD total collected dose of salbutamol was significantly higher with pMDI alone (352.35±23.41 µg) than AeroChamber Plus (196.57±13.32 µg, <em>p</em> &lt; 0.001) and MDI Plus (182.86±11.34 µg, <em>p</em> &lt; 0.001). Urinary salbutamol values at 30 min were significantly greater with AeroChamber Plus (14.61±4.36 µg, <em>p</em> &lt; 0.001) and MDI Plus (10.97±3.83 µg, <em>p</em> &lt; 0.01) compared to pMDI alone (5.92±1.07 µg). Urinary salbutamol at 24 h showed higher systemic bioavailability with pMDI alone (139.09±15.68 µg) versus when connected with both AeroChamber Plus and MDI Plus, 79.57±19.48, and 59.26±18.12 µg, <em>p</em> &lt; 0.001, respectively.</div></div><div><h3>Conclusion</h3><div>Compared to the pMDI alone, both spacers significantly enhanced lung delivery and reduced systemic absorption. Whilst the AeroChamber Plus® delivered slightly more medication to the lung, the MDI Plus® spacer offers a cost-effective alternative that is suitable for emergencies and outdoor use.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107215"},"PeriodicalIF":4.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Characteristics of contents in the upper gastrointestinal lumen after a standard high-calorie high-fat meal and implications for the in vitro drug product performance testing conditions” [Eur J Pharm Sci. 155 (2020) 105535]","authors":"Christina Pentafragka ,&nbsp;Maria Vertzoni ,&nbsp;Jennifer Dressman ,&nbsp;Mira Symillides ,&nbsp;Konstantinos Goumas ,&nbsp;Christos Reppas","doi":"10.1016/j.ejps.2025.107203","DOIUrl":"10.1016/j.ejps.2025.107203","url":null,"abstract":"","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107203"},"PeriodicalIF":4.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metastasis and angiogenesis: preclinical PET study on hepatocellular carcinoma (He/De) tumor models","authors":"Alexandra Barkóczi ,&nbsp;Zita Képes ,&nbsp;Judit P. Szabó ,&nbsp;Renáta Adél Dienes ,&nbsp;Péter Kálmán Károlyi ,&nbsp;Tamás Papp ,&nbsp;Ibolya Kálmán-Szabó ,&nbsp;Tamás Sass ,&nbsp;Gábor Opposits ,&nbsp;István Kertész ,&nbsp;István Hajdu ,&nbsp;György Trencsényi ,&nbsp;Ádám Deák","doi":"10.1016/j.ejps.2025.107211","DOIUrl":"10.1016/j.ejps.2025.107211","url":null,"abstract":"<div><div>The use of animal models to study tumorigenesis and metastatic spread seems crucial to discover novel diagnostic and therapeutic targets that inhibit tumor development and progression. In this study a preclinical metastasis model of hepatocellular carcinoma (He/De) was established to explore metastases formation and related angiogenic processes using positron emission tomography (PET) and angiogenesis specific radiopharmaceuticals. Approximately 8 ± 1 days after the subrenal capsule assay-based generation of the primary, secondary and tertiary transplanted metastatic He/De tumors in Fischer-344 rats, we used [¹⁸F]FDG, [⁶⁸Ga]Ga-NOTA-c(NGR) and [⁶⁸Ga]Ga-NODAGA-[c(RGD)]₂ for the <em>in vivo</em> PET imaging of tumor development and angiogenesis. [¹⁸F]FDG displayed the highest level of radioactivity among all investigated tracers. This pattern was consistent across all neoplastic lesions in each of the three transplantations. Comparing the two ⁶⁸Ga-labelled probes, the NGR compound showed significantly higher accumulation in the subrenally growing primary/secondary/tertiary He/De tumors <em>(p</em> <em>≤</em> <em>0.05)</em> and related parathymic lymph node metastases (PTLNs, <em>p</em> <em>≤</em> <em>0.01</em>) that could indicate higher expression level for aminopeptidase N/CD13 than for RGD-binding α_vβ₃ integrin. Progressive increase in the [¹⁸F]FDG, [⁶⁸Ga]Ga-NOTA-c(NGR) and [⁶⁸Ga]Ga-NODAGA-[c(RGD)]₂ uptakes of both the subrenally growing He/De tumors and the PTLNs during the serial transplantations may imply increasing aggressivity. Overall, the currently developed experimental system provides a feasible platform for further investigation of metastatic spread.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107211"},"PeriodicalIF":4.7,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precipitation as key parameter for early oral drug absorption predictions, Part II: Development of a predictive model","authors":"Sara Mayer ,&nbsp;Katharina Krollik ,&nbsp;Christian Wagner ,&nbsp;Johannes Wittmann ,&nbsp;Andreas Lehmann","doi":"10.1016/j.ejps.2025.107212","DOIUrl":"10.1016/j.ejps.2025.107212","url":null,"abstract":"<div><div>Accurate absorption predictions for new chemical entities (NCEs) are key in drug discovery, as they enable the early identification of compounds with suboptimal absorption characteristics. Common methodologies, such as the biopharmaceutical classification system (BCS), often lack quantitative insights, or they require extensive datasets at early stages, as seen in Physiologically Based Biopharmaceutics Modeling (PBBM). Furthermore, existing tools frequently overlook the impact of precipitation of weakly basic drugs on human absorption. To bridge this gap, we developed a novel oral absorption prediction tool that uses easily obtainable in vitro assay results while systematically investigating the relationship between in vitro precipitation and in vivo absorption. The underlying dataset, which is compiled in Part I of this study, includes in vivo human absorption data alongside in vitro permeability, solubility, and precipitation data for 17 basic compounds. In this part of the study, the dataset underwent a comprehensive statistical analysis. While regression analysis proved inadequate, a decision tree using the Classification and Regression Trees (CART) algorithm was constructed. The assessments from this algorithm led to the inclusion of both precipitation and permeability in the final decision tree, while solubility was excluded. This finding underscores the critical role and added value of in vitro precipitation compared to solubility. This intuitive tool is particularly well-suited for drug discovery, as it facilitates ranking and selection of drug candidates based on their oral absorption characteristics. Additionally, it can be easily adapted by other researchers, allowing for the incorporation of various in vitro assays and larger datasets to meet specific research needs. This flexibility paves the way for future advancements in the field.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"213 ","pages":"Article 107212"},"PeriodicalIF":4.7,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precipitation as key parameter for early oral drug absorption predictions, Part I: Acquisition of critical data","authors":"Sara Mayer ,&nbsp;Christian Wagner ,&nbsp;Andreas Lehmann ,&nbsp;Zhizhou Fang ,&nbsp;Werner Weitschies ,&nbsp;Katharina Krollik","doi":"10.1016/j.ejps.2025.107210","DOIUrl":"10.1016/j.ejps.2025.107210","url":null,"abstract":"<div><div>Despite recent advancements in the development of in vitro precipitation assays for weakly basic drugs, their relevance for predicting in vivo oral absorption remains ambiguous, highlighting the need for further research. The objective of this study was to develop a predictive tool for drug absorption of basic drugs, grounded in data derived from in vitro solubility, permeability, and precipitation assays which is particularly suited for application in drug discovery. The study aimed to compile a comprehensive dataset comprising in vitro solubility, permeability, and precipitation data, and in vivo absorption data for a set of 17 model compounds. The dataset was designed to serve as foundation for the development of an absorption prediction tool specifically tailored for drug discovery. For this purpose, solubility and permeability data were measured using a consistent experimental set-up for each, ensuring data comparability. Furthermore, a miniaturized precipitation assay (µPA) was developed that enables streamlined screening of drug candidates, thereby enhancing the lead optimization process during drug discovery. In vivo absorption data for the 17 model compounds were gathered through a comprehensive literature review, addressing the inherent challenges associated with acquiring high-quality in vivo absorption data. The results of this study indicate a decent relationship between the extent of precipitation in vitro, and the fraction of a drug absorbed in vivo. In-depth statistical analysis of the dataset and the development of the absorption prediction tool will be described in a subsequent publication.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"213 ","pages":"Article 107210"},"PeriodicalIF":4.7,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo metabolic pathways and tissue distribution of pharmaceutical excipient polysorbate 80 using ultra-high performance liquid chromatography-high resolution mass spectrometry analysis","authors":"Zhe Wang ,&nbsp;Yutong Sun ,&nbsp;Xinjian Li,&nbsp;Qi Liu,&nbsp;Jinlan Zhang","doi":"10.1016/j.ejps.2025.107208","DOIUrl":"10.1016/j.ejps.2025.107208","url":null,"abstract":"<div><div>Polysorbate 80 (PS80) is a pharmaceutical excipient widely used in injectables, antibody drugs and vaccines. Due to complex composition, its <em>in vivo</em> analysis is challenging, and there are few studies on its metabolic characteristics and pathways <em>in vivo</em>. In this study, a novel analytical method using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC<img>HRMS) was developed to comprehensively characterize the components and metabolites of PS80 in biological samples with “omics analysis” feature. Based on this method, 272 components and metabolites belonging to 11 types were identified in rats after intravenous injection of PS80, with POE sorbitan (44.5 %/43.6 %, female/male), POE isosorbitan (22.6 %/23.1 %, female/male), POE (7.3 %/7.4 %, female/male), POE sorbitan dioleate (13.9 %/14.1 %, female/male), and POE sorbitan trioleate (8.4 %/8.3 %, female/male) having higher plasma exposure according to their AUC_(0-t) proportion. The esterified components were rapidly hydrolyzed stepwise from tetra-esterified, tri-esterified, di-esterified, and mono-esterified to non-esterified metabolites in the circulatory system. The hydrolysis rate was related to their parent nucleus and degree of esterification: POE oleate&gt;POE isosorbitan oleate&gt;POE sorbitan oleate; mono-esterification&gt;tri-esterification&gt;di-esterification. PS80 metabolites were rapidly and widely distributed in various tissues and organs, with particularly high exposure in immune organs, such as spleen, thymus, and lymphaden. It was first found that the spleen had high exposure and slow clearance of the PS80 metabolites POE sorbitan and POE isosorbitan, and was significantly enriched in the esterified metabolites POE sorbitan dioleate and POE sorbitan monooleate. Ultimately, the non-esterified metabolites were excreted in urine primarily, with some via bile and feces. This study elucidated the exposure characteristics and metabolic pathways of PS80 <em>in vivo</em> for the first time, and it was helpful for the development, quality control and clinical safety studies of related formulations.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107208"},"PeriodicalIF":4.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the potential of chlorido[N,N'-bis(salicylidene)-1,2-phenylenediamine]iron(III): Exploring delivery through lipid-based nanocarriers","authors":"Marlene Ramona Schmidt ,&nbsp;Astrid Dagmar Bernkop-Schnürch ,&nbsp;Daniel Stengel ,&nbsp;Magnus Andre Kiechle ,&nbsp;Khush Bakhat Afzal ,&nbsp;Anna Seybold ,&nbsp;Martin Hermann ,&nbsp;Brigitte Kircher ,&nbsp;Andreas Bernkop-Schnürch","doi":"10.1016/j.ejps.2025.107206","DOIUrl":"10.1016/j.ejps.2025.107206","url":null,"abstract":"<div><h3>Aim</h3><div>This research outlines the development of an innovative delivery system for administration of chlorido[<em>N,N</em>'-bis(salicylidene)-1,2-phenylenediamine]-iron(III) salophene – designated Iron(III) Salophene (Fe³⁺SP).</div></div><div><h3>Methodology</h3><div>The identity of Fe³⁺SP was confirmed using FTIR, and its lipophilicity (log P) was quantified by HPLC. Fe³⁺SP was then incorporated into lipid-based nanocarriers (LBNCs) with a lipid matrix of triglycerides of caprylic/capric acid (45.4 %; v/v), phosphatidylcholine (36.4 %; m/v) and benzyl alcohol (18.2 %; v/v) as solvent. Metabolic activity was investigated via the MTT assay on various cell lines, and cellular uptake was analyzed by confocal laser scanning microscopy using different dyes.</div></div><div><h3>Results</h3><div>The log P value of 1.8 for the Fe³⁺SP-complex confirmed sufficient lipophilicity for incorporation into lipid-based nanocarriers. Ultrasonic treatment significantly reduced particle size from 1000 nm to about 200 nm and improved particle uniformity from 1.0 to about 0.2 for blank and Fe³⁺SP LBNCs. Different stability studies showed consistent droplet sizes in various buffer systems (150–230 nm) over 14 days, and uniform particle distribution (∼0.2) confirmed stability in physiological media over 48 h. TEM analysis revealed that Fe³⁺SP maintains uniform morphology and enhances stability, leading to consistent particle size and shape, promoting cellular uptake. Compared to Fe³⁺SP in DMSO, the LBNC-loaded formulation exhibited a five-fold higher effect on cancer cell lines at a similar cellular uptake, indicating higher efficacy.</div></div><div><h3>Conclusion</h3><div>These findings suggest that LBNCs offer a promising platform for the oral delivery of Fe³⁺SP, with significant advantages over conventional delivery systems.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107206"},"PeriodicalIF":4.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peptide drug delivery: Permeation behaviour and intracellular fate of hydrophobic ion pairs in self-emulsifying drug delivery systems","authors":"Martyna Truszkowska ,&nbsp;Melanie Lena Ebert ,&nbsp;Khush Bakhat Afzal ,&nbsp;Váradi Györgyi ,&nbsp;Andreas Bernkop-Schnürch","doi":"10.1016/j.ejps.2025.107207","DOIUrl":"10.1016/j.ejps.2025.107207","url":null,"abstract":"<div><div>This study aimed to investigate the permeation behaviour and intracellular fate of hydrophobic ion pairs (HIP).</div><div>HIP were formed by combining a daptomycin-derived model peptide (DD) with ethyl lauroyl arginate (ELA) and lipophilic fluorescent dye 4-(4-dihexadecylaminostyryl)-N-methylpyridinium iodide (DiA). A representative HIP (DD: ELA: DiA, molar ratio 1:4:0.5) was incorporated into self-emulsifying drug delivery systems (SEDDS) and characterized for size, zeta potential, stability, hemolytic activity, cytotoxicity, and cellular uptake. Permeability was assessed using the Parallel Artificial Membrane Permeability Assay (PAMPA) model and Caco-2 monolayers.</div><div>SEDDS exhibited droplet sizes below 200 nm, a polydispersity index (PDI) &lt; 0.4, positive surface charges, and high stability. Hemolysis studies indicated potential for endosomal escape, while dose-dependent toxicity became apparent after 4 and 24 h of incubation. Flow cytometry revealed enhanced cellular uptake: HIP and SEDDS increased internalization of DD by 12- and 32-fold, compared to free peptide. Permeation studies demonstrated marked improvements in DD transport. In the PAMPA assay, HIP and SEDDS increased passive diffusion by 2.8<strong>-</strong> and 6.5-fold. Similarly, in the Caco-2 model, HIP and SEDDS enhanced permeation by 17<strong>-</strong> and 57-fold, compared to free DD. DiA permeation remained minimal, suggesting that HIP disassociates intracellularly, allowing selective release of the peptide.</div><div>These findings confirm that HIP enhances membrane permeation of DD and dissociates after uptake. The combination of HIP and SEDDS presents a robust strategy for improving the oral bioavailability of peptide therapeutics.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107207"},"PeriodicalIF":4.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymeric material based on cystamine-protoporphyrin IX connection in PLGA of potential utility in photodynamic therapy - preparation, physicochemical properties, and biological activity","authors":"Patrycja Koza ,&nbsp;Marcin Wysocki ,&nbsp;Malgorzata Kucinska ,&nbsp;Julia Pospieszna ,&nbsp;Bartłomiej Kost ,&nbsp;Maciej Stawny ,&nbsp;Aleksander Smolarkiewicz-Wyczachowski ,&nbsp;Dariusz T. Mlynarczyk ,&nbsp;Marta Ziegler-Borowska ,&nbsp;Tadeusz Biela ,&nbsp;Lukasz Sobotta ,&nbsp;Tomasz Koczorowski ,&nbsp;Marek Murias ,&nbsp;Tomasz Goslinski","doi":"10.1016/j.ejps.2025.107209","DOIUrl":"10.1016/j.ejps.2025.107209","url":null,"abstract":"<div><div>By the use of suitable delivery systems and pharmaceutical formulations, improved transportation of photosensitizers to cancer cells in photodynamic therapy can be achieved. The aim of our study was to demonstrate controlled, redox-triggered release of a photosensitizer by developing a redox- and photo-responsive polymeric carrier system based on poly(lactic-<em>co</em>-glycolic acid) functionalized with cystamine and protoporphyrin IX, which could serve as a model for potential use in photodynamic therapy.</div><div>During the study, polymeric materials based on cystamine-protoporphyrin IX combination incorporated in poly(lactic-<em>co</em>-glycolic acid) were obtained, characterised in physicochemical studies and subjected to biological assessment. The presence of cystamine enabled the PPIX release in the presence of thiol triggers. The physicochemical characterisation of the new material was performed using UV–Vis, IR, NMR spectroscopies, X-Ray diffraction, and thermogravimetric analysis. The size and morphology of the obtained material were determined using nanoparticle tracking analysis, as well as SEM and TEM microscopy. The photochemical properties and stability of the material were analysed by establishing the singlet oxygen generation and photodecomposition quantum yields.</div><div>The acute toxicity of modified polymeric material was determined using the Microtox® test, whereas cyto- and photocytotoxicities were assessed <em>in vitro</em> on the human prostate cancer cell line (LNCaP) and human lung fibroblast (MRC-5). The polymer components, cystamine and PLGA, did not affect cell viability on their own, neither upon irradiation nor in the absence of light. The obtained polymeric material based on a protoporphyrin IX-cystamine molar ratio of 1:1 in PLGA could be considered a prospective formulation for PDT.</div><div>The novelty of our study lies in the design of a dual-responsive (redox and light) PLGA-based carrier system encapsulating protoporphyrin IX and a redox-cleavable linker, enabling controlled, photo-triggered release of the photosensitizer.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107209"},"PeriodicalIF":4.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transport across membrane meets biophysics to unveil the mechanism of action of a novel gH625 analogue","authors":"Rosa Bellavita ,&nbsp;Annalisa Pecoraro ,&nbsp;Sara Palladino ,&nbsp;Camilla Danisi ,&nbsp;Annarita Falanga ,&nbsp;Gabriella D’Auria ,&nbsp;Lucia Falcigno ,&nbsp;Giulia Russo ,&nbsp;Stefania Galdiero ,&nbsp;Annapina Russo","doi":"10.1016/j.ejps.2025.107204","DOIUrl":"10.1016/j.ejps.2025.107204","url":null,"abstract":"<div><div>Cell-penetrating peptides are widely used in drug delivery for their ability to facilitate the transport of nanomaterials inside the cell. We previously studied the gH-625 for its ability to cross cell membranes, delivering various cargos into different cell types. In this study, since gH-625 suffers from low proteolytic stability, we identified the main cleavage sites after incubation with the enzyme chymotrypsin, and <span>l</span>-amino acids at these sites were replaced with their <span>d</span>-enantiomers, which share similar physicochemical properties but have distinct biological roles. Four peptides, namely gH-w10, gH-l7, gH-y13, and gH-combi, were designed and synthesized. Their biosafety profiles were evaluated in both normal and cancer cell lines and no significant toxic effects were revealed at the tested concentrations. Subsequently, we assessed their cell-penetrating ability by evaluating cellular uptake through fluorescence microscopy and investigated their mechanism of action in a model system of liposomes, measuring fusogenic activity, peptide insertion into the lipid bilayer, and leakage activity. The impact of the <span>d</span>-amino acid substitution on secondary structure was explored by circular dichroism and nuclear magnetic resonance studies. Finally, <em>in vitro</em> safety profiling data of the gH-625 and its most promising derivative gH-combi were further confirmed <em>in vivo</em> using a chicken embryo model.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"212 ","pages":"Article 107204"},"PeriodicalIF":4.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}