European Journal of Pharmaceutical Sciences最新文献

{"title":"Linagliptin attenuates kidney cancer in rats via AMPK activation and suppression of YAP/TAZ/HIF-1α signaling","authors":"Tahani Saeedi ,&nbsp;Mohannad Almikhlafi ,&nbsp;Hossein M Elbadawy ,&nbsp;Muayad S Albadrani ,&nbsp;Rehab F Abdel-Rahman ,&nbsp;Gihan F. Asaad ,&nbsp;Fatma A Ibrahim ,&nbsp;Aya A. Shokry ,&nbsp;Tuba Esatbeyoglu ,&nbsp;Sherif M. Afifi ,&nbsp;Hany M Fayed ,&nbsp;Marawan A. Elbaset","doi":"10.1016/j.ejps.2025.107393","DOIUrl":"10.1016/j.ejps.2025.107393","url":null,"abstract":"<div><div>This study investigated the renoprotective action of linagliptin compared to doxorubicin against thioacetamide (TAA) and diethyl nitrosamine (DEN)-induced renocarcinogenesis in a rat model. Male Wistar rats were divided into control, renocarcinogenesis (RCC), doxorubicin group (7.5 mg/kg, i.p., once weekly), and linagliptin (Lina) groups (3 and 6 mg/kg/day, p.o.). The experiment included renal function parameters, oxidative stress markers, and predominant molecular pathways involved in renal pathogenesis. The RCC model significantly impaired renal function, as reflected in elevated serum levels of urea and creatinine. It also resulted in elevated oxidative stress, as reflected in increased malondialdehyde (MDA) content and decreased glutathione and superoxide dismutase (GSH and SOD) activities. The model disrupted several molecular pathways, including the AMP-activated protein kinase (AMPK) pathway, and enhanced oncogenic and inflammatory markers such as Yes-associated protein/ Transcriptional coactivator with PDZ-binding motif/ Hypoxia-inducible factor 1-alpha (YAP/TAZ/ HIF-1α), nuclear factor erythroid 2-related factor 2/ Sirtuin 1(Nrf2/SIRT1), and signal transducer and activator of transcription 3 (STAT3). Treatment with linagliptin, particularly the high dose (6 mg/kg/day), was found to be superior to doxorubicin treatment in terms of correction of renal function and markers of oxidative stress. Linagliptin effectively regulated the AMPK pathway, reduced markers of inflammation, restored the expression of genes with key roles in renal protection, reduced proliferating Cell Nuclear Antigen (PCNA), and elevated Caspase-3. The high dose of linagliptin exhibited superior results in most of the parameters, which approached control levels more than those with the lower dose and doxorubicin. These findings demonstrate that linagliptin, especially at 6 mg/kg/day, exhibits significant renoprotective activities through multifarious mechanisms involving antioxidant action and regulation of key molecular pathways. The present study presents evidence for the potential therapeutic application of linagliptin in renal manifestations of renocarcinogenesis.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107393"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667657","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":"Comparing iron sucrose and ferric carboxymaltose interactions with murine and human macrophages: Focus on the lysosomal compartment","authors":"Mauro Sousa de Almeida ,&nbsp;Amélie Bazzoni ,&nbsp;Sandor Balog ,&nbsp;Kata Dorbic ,&nbsp;Céline Loussert-Fonta ,&nbsp;Aura Maria Moreno-Echeverri ,&nbsp;Jules Duruz ,&nbsp;Jorge Larios ,&nbsp;Anne-Marinette Cao ,&nbsp;Amy Barton Alston ,&nbsp;Reinaldo Digigow ,&nbsp;Beat Flühmann ,&nbsp;Alke Petri-Fink ,&nbsp;Barbara Rothen-Rutishauser","doi":"10.1016/j.ejps.2025.107390","DOIUrl":"10.1016/j.ejps.2025.107390","url":null,"abstract":"<div><div>Intravenous iron drugs are commonly used in the treatment of iron deficiency/iron deficiency anaemia. However, the cellular mechanisms underlying the uptake of these complexes remain poorly understood. This study examines the interaction of two iron complexes, iron sucrose and ferric-carboxymaltose, with murine J774A.1 and human M2a macrophages, focusing on their uptake and localization within lysosomal compartments at various time points: 45 min, 6 h, 24 h, and 5 days. We employed multiple analytical methods, including Prussian blue staining and transmission electron microscopy, to assess the intracellular iron complexes. In addition, the stability of the two complexes in cell culture medium and artificial lysosomal fluid was assessed by dynamic light scattering and transmission electron microscopy. A formation of larger aggregates for both complexes in cell culture medium was observed, likely due to interactions with serum proteins. The analysis in artificial lysosomal fluid revealed a slight, but not statistically significant, decrease in hydrodynamic diameter. Upon interaction with macrophages, our results demonstrate that iron sucrose is internalized more rapidly by both macrophage cell types compared to ferric carboxymaltose. Furthermore, the detection of ferric ions within intracellular and intralysosomal compartments occurs at a later time point following macrophage exposure to ferric carboxymaltose, suggesting slower internalization in comparison to iron sucrose. Our findings suggest that the two complexes remain intact upon reaching macrophages and, after internalization, are localized within intracellular vesicles, indicating endocytosis as the primary uptake mechanism. Iron sucrose was internalized more rapidly in comparison to ferric carboxymaltose by both macrophage types, whereas a decrease in metabolic activity was only observed for the J774A.1 macrophages in the presence of high iron sucrose concentration, <em>i.e.</em>, 1mg/mL iron. These findings provide new insights into the dynamics of different iron-carbohydrate complexes on cellular uptake and may contribute to optimizing future drug designs.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107390"},"PeriodicalIF":4.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647884","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":"Vancomycin release kinetics for treatment of bone tissue infection: design of a loaded scaffold and evaluation of a dynamic model","authors":"Antoine Recorda ,&nbsp;Cynthia Abane ,&nbsp;Emeline Renaudie ,&nbsp;Patricia Pascaud-Mathieu ,&nbsp;Arnaud Beaumont ,&nbsp;Karine Giry ,&nbsp;Sylvie Delebassée ,&nbsp;Amandine Magnaudeix ,&nbsp;Betty Laverdet ,&nbsp;Chantal Damia","doi":"10.1016/j.ejps.2025.107391","DOIUrl":"10.1016/j.ejps.2025.107391","url":null,"abstract":"<div><div>The development of local drug delivery systems (DDS) has emerged as a promising strategy for targeted therapeutic applications, enabling high drug concentrations at specific sites while minimizing systemic toxicity. However, the evaluation of drug release kinetics remains challenging due to the limitations of current <em>in vitro</em> models, which often fail to replicate physiological conditions. To address this issue, dynamic models, such as flow perfusion bioreactors, offer a more realistic approach to studying DDS, particularly in cases where prolonged drug release is required, such as the prevention of surgical site infections (SSI) in bone grafts. In this study, a macroporous hydroxyapatite (HA) scaffold was designed through robocasting, an additive manufacturing technique, to obtain a bone substitute with a controlled macroporous architecture. HA was chosen for its chemical similarity to the mineral phase of bone, its non-biodegradability, and its ability to support antibiotic loading and release. Vancomycin, a broad-spectrum antibiotic commonly used against <em>Staphylococcus aureus</em>, was incorporated into a thermosensitive chitosan hydrogel to regulate its release kinetics. The loaded scaffolds were evaluated using a perfusion bioreactor to model the bone microenvironment. The antibiotic release profile was determined using high-performance liquid chromatography (HPLC) and an iterative algorithm. The objective is to establish a proof of concept and demonstrate the relevance of a dynamic, animal-free model for studying the kinetics of local antibiotic release. The results showed that the combination of a macroporous HA scaffold and a chitosan hydrogel enabled sustained antibiotic release over time. Furthermore, <em>in vitro</em> antibacterial assays confirmed the efficacy of the released vancomycin against <em>Staphylococcus aureus</em>. This study highlights the potential of using perfusion bioreactors and additive manufacturing techniques to develop physiologically relevant DDS models, ultimately contributing to the refinement of antibiotic delivery strategies.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107391"},"PeriodicalIF":4.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654047","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":"Application of a forward design-based multi-attribute decision-making method in quality assessment in pharmaceutical tablet manufacturing","authors":"Xinhao Wan ,&nbsp;Ming Yang ,&nbsp;Zhijian Zhong ,&nbsp;Xiaoqing Zhou ,&nbsp;Xuecheng Wang ,&nbsp;Qing Tao ,&nbsp;Zhenfeng Wu","doi":"10.1016/j.ejps.2025.107392","DOIUrl":"10.1016/j.ejps.2025.107392","url":null,"abstract":"<div><div>With the modernization of the pharmaceutical industry and increasingly stringent regulatory requirements, ensuring the quality and process stability of pharmaceutical tablets has become a critical challenge. In particular, chewable tablets, as a unique type of oral solid dosage form designed to be chewed before swallowing, require special attention to mechanical properties and sensory attributes such as texture, mouthfeel, and taste acceptability. This study aims to implement a forward design-based multi-attribute decision-making (MADM) framework for systematic and accurate multi-criteria quality assessment and prediction of pharmaceutical chewable tablets. Tablets were produced using batch-based tableting technology, and critical quality attributes—including weight variation, friability, porosity, and hardness—were systematically evaluated under varying process conditions. Tensile strength was employed as an external validation index. To overcome the limitations of traditional evaluation methods, the proposed MADM framework incorporates a game theory (GT)-based combinatorial weighting strategy, effectively integrating subjective experience-based judgment with objective data-driven metrics. In addition, a backpropagation neural network (BPNN) model was developed to capture the nonlinear relationships between process parameters and the comprehensive quality index. Compared to conventional weighting approaches such as the analytic hierarchy process (AHP), entropy method (EM), and mean-based weighting, the GT-based strategy demonstrated superior performance in terms of evaluation robustness and accuracy. The MADM results showed strong agreement with the tensile strength data, confirming the reliability and consistency of the evaluation framework. Furthermore, the BPNN model achieved high prediction accuracy, providing solid quantitative support for process optimization. Overall, the proposed method offers a robust and generalizable solution for multi-criteria quality assessment and prediction of pharmaceutical chewable tablets. When integrated with industrial information systems, it enables data-driven optimization, intelligent quality control, and automation, thereby contributing to the advancement of smart pharmaceutical manufacturing.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107392"},"PeriodicalIF":4.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654019","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":"Nortriptyline-targeted siRNA-loaded liposomes: Design, affinity, biodistribution, and bioactivity in a murine Herpes Simplex Virus 1 corneal infection model","authors":"Doaa Jbara-Agbaria ,&nbsp;Neethi C Thathapudi ,&nbsp;Marc Groleau ,&nbsp;Majd Agbaria ,&nbsp;Marie-Claude Robert ,&nbsp;Natalia Callai Da Silva ,&nbsp;Sebastien Talbot ,&nbsp;Janet Laganiere ,&nbsp;May Griffith ,&nbsp;Gershon Golomb","doi":"10.1016/j.ejps.2025.107388","DOIUrl":"10.1016/j.ejps.2025.107388","url":null,"abstract":"<div><div>Herpes simplex virus type 1 (HSV1) establishes latency in the trigeminal ganglia and reactivates to cause recurrent infections and severe complications, including herpes simplex keratitis (HSK), the leading cause of infectious corneal blindness in developed countries. We developed and characterized a targeted siRNA delivery system designed to suppress HSV1 by silencing the immediate-early gene ICP0, which encodes a protein essential for lytic infection and viral reactivation. To enhance neuronal accumulation, siRNA-loaded liposomes were decorated with nortriptyline (NTP), a ligand with high affinity for neuronal cells, including those in the trigeminal ganglia. The liposomes were optimized to exhibit nanoscale size, low polydispersity, neutral surface charge, high siRNA loading, spherical morphology, and long-term shelf stability. Studies in cell lines confirmed efficient internalization with good tolerability, and targeted liposomes showed enhanced binding to differentiated PC‑12 neuronal cells, competitively inhibited by free NTP, supporting their targeting specificity. Following retro-orbital administration in mice, NTP-targeted siHSV1 liposomes preferentially accumulated in the trigeminal ganglia. Antiviral efficacy was further assessed by topical application of siHSV1‑loaded liposomes within a biocompatible hydrogel in a murine HSV1 corneal perforation model of HSK. In the corneal limbus, targeted liposomes produced a significant reduction in viral load, whereas in the contralateral trigeminal ganglia, they significantly reduced viral load with a pronounced trend toward decreased ICP0 expression. These results demonstrate the feasibility of using NTP-mediated targeting ligand and support the potential of this delivery platform for treating latent HSV1, warranting further optimization for improved therapeutic efficacy.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107388"},"PeriodicalIF":4.7,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145631484","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":"Development of a controlled-release tofacitinib formulation using acid-sensitive pore-forming components for an osmotic drug delivery system","authors":"Jin Ah Lee ,&nbsp;Yun Jung Lee ,&nbsp;Jeong A Seong ,&nbsp;Myung Kwan Chun ,&nbsp;Kwon Yeon Weon","doi":"10.1016/j.ejps.2025.107389","DOIUrl":"10.1016/j.ejps.2025.107389","url":null,"abstract":"<div><div>Acid-sensitive ingredient porosity osmotic drug delivery systems (AID) are a simplified and scalable alternative to conventional ODDS. In the current study, the tofacitinib-loaded AID formulation was optimized using an I-optimal mixture design. The three coating excipients examined as independent variables were cellulose acetate (X₁; 25.8–43.8 %), sodium bicarbonate (X₂; 20.0–30.0 %), and hydroxypropyl cellulose (X₃; 26.3–46.3 %). Response variables included cumulative drug release at 2 h (Y₁), 4 h (Y₂), and 8 h (Y₃), as well as the percentage of residual drug after 8 h (Y₄), which were analyzed using a quadratic model within the I-optimal framework. The coefficient of determination (R²) values for Y₁, Y₂, Y₃, and Y₄ were 0.79, 0.74, 0.55, and 0.48, respectively. The optimized AID exhibited zero-order drug release kinetics (R² = 0.9931), with a release rate constant (K₀) of 0.20 h⁻¹, indicating a consistent and controlled release profile throughout the evaluation period. Pharmacokinetic studies indicated no significant lag time for the AID, while Xeljanz® XR 11 mg exhibited an initial lag time of approximately 0.64 h, consistent with the characteristics of conventional ODDS technologies. Maximum plasma concentrations (C_max) were 75.7 ± 40.8 ng/mL for Xeljanz® XR 11 mg and 79.4 ± 37.1 ng/mL for AID. The areas under the plasma concentration-time curve were 610.0 ± 187.5 ng/mL for Xeljanz® XR 11 mg and 586.1 ± 210.5 ng/mL for AID. Times to maximum plasma concentration were 5 h for Xeljanz® XR 11 mg and 2 h for AID. Collectively, this modified approach reduces the initial lag time and allows for faster drug action.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107389"},"PeriodicalIF":4.7,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145631391","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 “Effects of nonsense genetic variants on OATP1B1 expression and transport activity in vitro” [European Journal of Pharmaceutical Sciences 215 (2025) 107322]","authors":"Wilma Kiander ,&nbsp;Hatam Rashidpour ,&nbsp;Mikko Gynther ,&nbsp;Kati-Sisko Vellonen ,&nbsp;Mikko Neuvonen ,&nbsp;Laura Vesalainen ,&nbsp;Kristiina M. Huttunen ,&nbsp;Mikko Niemi ,&nbsp;Heidi Kidron","doi":"10.1016/j.ejps.2025.107381","DOIUrl":"10.1016/j.ejps.2025.107381","url":null,"abstract":"","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107381"},"PeriodicalIF":4.7,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586519","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":"Uncertainties in drug dissolution tests - identification and CFD evaluation of factors limiting the accuracy of the USP2 test","authors":"Normunds Jekabsons ,&nbsp;Sabīne Upnere ,&nbsp;Artūrs Lācis ,&nbsp;Ance Bārzdiņa ,&nbsp;Daniela Paula Prudņikova ,&nbsp;Una Lote Vītoliņa ,&nbsp;Baiba Mauriņa ,&nbsp;Agnese Brangule","doi":"10.1016/j.ejps.2025.107387","DOIUrl":"10.1016/j.ejps.2025.107387","url":null,"abstract":"<div><div>Accurate USP2 paddle dissolution testing is crucial for the quality characterisation, development, and research of solid‑dosage forms, but measurement uncertainties, particularly during the initial flow‑build‑up phase, can mask batch‑to‑batch differences. This work focuses on Computational Fluid Dynamics (CFD) using high-resolution simulations to identify and quantify the main factors contributing to uncertainty in the dissolution of single-component paracetamol tablets. CFD simulations were performed using the OpenFOAM toolkit using a custom solver that simultaneously resolves Navier–Stokes flow and the convective‑diffusive transport of paracetamol. The dissolution process was modelled using the Direct Numerical Simulation and the Smagorinsky-Lilly LES formulation with Van Driest wall damping. Targeted dissolution experiments were used to validate the numerical predictions. Laboratory-prepared tablets (500 ± 1.6 mg) were tested under three configurations: (i) free floating, (ii) magnetically fixed, and (iii) fixed with the tablet bottom coated to suppress rear‑face dissolution. Tests were conducted in a USP2 apparatus at paddle speeds of 25, 50, and 75 RPM, with sampling from 0.5 min to 40 min to capture the time dynamics. The simulated concentration and integral mass fluxes matched experimental dissolution rates.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107387"},"PeriodicalIF":4.7,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596231","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":"Pulmonary delivery of siRNA lipoplexes and lipid nanoparticles using a vibrating mesh nebuliser","authors":"Michael T. Neary ,&nbsp;Lianne M. Mulder ,&nbsp;Ciaran O. Leime ,&nbsp;Ronan MacLoughlin ,&nbsp;Brunella Grassiri ,&nbsp;Łukasz Baranowski ,&nbsp;Piotr S. Kowalski ,&nbsp;Abina M. Crean ,&nbsp;Katie B. Ryan","doi":"10.1016/j.ejps.2025.107386","DOIUrl":"10.1016/j.ejps.2025.107386","url":null,"abstract":"<div><div>Inhalation via nebulisation is a promising method to deliver high concentrations of siRNA to the lung epithelium in a direct and non-invasive manner for the treatment of numerous respiratory-related illnesses. However, nebulisation can be destructive towards siRNA nanocarriers leading to loss of siRNA and a diminished therapeutic outcome. Herein, we sought to explore how the nebulisation process, including adjustments in aerosol droplet size impacts the physicochemical properties of several lipid-based siRNA nanocarrier formulations. These included PEGylated and non-PEGylated cationic DOTAP-based lipoplexes (LPXs) and C12–200 based lipid nanoparticles (LNPs). Two Aerogen® Pro vibrating mesh nebuliser devices with capacities to generate aerosols of differing volumetric mean diameters (VMD) were utilised. The aerosol droplet sizes for the different siRNA formulations were 4.80 to 4.89 µm (High VMD device) and 3.56 to 3.59 µm (Low VMD device) demonstrating that the emitted droplet size distribution was consistent across multiple siRNA nanocarrier types. Further, the formulations exhibited mass median aerodynamic diameters (MMAD) of 4.03 – 4.84 µm (High VMD device) indicating their potential for targeting siRNA lung deposition. Aggregation in both lipoplex formulations and a significant reduction in LNPs’ siRNA encapsulation efficiency were observed. <em>In vitro</em> studies in Firefly luciferase (Fluc) expressing alveolar A549 cells demonstrated that cell viability and Fluc knockdown were generally unaffected by nebulisation. However, Fluc knockdown varied depending on formulation type and was highest for LNPs (93 %) and lowest for the PEGylated LPXs (max 30 %). Overall, this study shows that aerosols with consistent droplet size can be generated but the choice of nanocarrier impacts the stability and delivery efficacy and requires careful consideration for efficient nebulised siRNA delivery.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107386"},"PeriodicalIF":4.7,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582080","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":"Impact of yeast cell wall incorporation on the mucoadhesion, stability, oral permeability and release profile of alginate/whey protein beads loaded with insulin","authors":"Emmanuelle Lainé ,&nbsp;Valerie Hoffart ,&nbsp;Imen Dhifallah ,&nbsp;Ghislain Garrait ,&nbsp;Eric Beyssac","doi":"10.1016/j.ejps.2025.107385","DOIUrl":"10.1016/j.ejps.2025.107385","url":null,"abstract":"<div><div>This study aimed to evaluate the impact of incorporating yeast cell wall (YCW) into alginate/whey protein (ALG/WP) particles as a strategy to improve oral insulin delivery. Insulin-loaded particles were produced by an extrusion–gelation process with or without YCW, and their physicochemical, mucoadhesive, and permeability properties were assessed <em>in vitro, ex vivo</em>, and <em>in vivo</em>. The inclusion of YCW increased the viscosity of the polymeric solution, resulting in more cohesive particles and a significant reduction in insulin loss during coating. Encapsulation efficiencies ranged from 65 to 99%. However, YCW did not significantly affect particle size or the release mechanism, which remained diffusion-controlled. Although YCW-containing beads exhibited enzyme inhibitory and mucoadhesive properties, insulin protection against enzymatic degradation was similar to that of control beads. YCW moderately enhanced insulin permeability in Caco-2 cell monolayers without cytotoxicity, consistent with a reversible reduction of transepithelial electrical resistance. This effect did not translate into a measurable increase in insulin absorption in ex vivo duodenum or <em>in vivo</em> duodenal administration, indicating that its contribution as an absorption enhancer is limited under physiologically complex conditions.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107385"},"PeriodicalIF":4.7,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573337","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}