European Journal of Pharmaceutical Sciences最新文献

{"title":"Erratum to “The fourth-generation EGFR tyrosine kinase inhibitor BLU-945 resensitizes ABCG2-overexpressing multidrug-resistant non-small cell lung cancer cells to cytotoxic anticancer drugs” [European Journal of Pharmaceutical Sciences (2025) 107337]","authors":"Yen-Ching Li , Bing-Huan Lin , Megumi Murakami , Yu-Shan Wu , Tai-Ho Hung , Suresh. V. Ambudkar , Chung-Pu Wu","doi":"10.1016/j.ejps.2025.107384","DOIUrl":"10.1016/j.ejps.2025.107384","url":null,"abstract":"","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"216 ","pages":"Article 107384"},"PeriodicalIF":4.7,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687207","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":"Synthesis, in vitro characterization and biopharmaceutical evaluation of a novel phosphate prodrug of sorafenib","authors":"Simon Hoang Dinh ,&nbsp;Christian Ding Fisker ,&nbsp;Juulia Järvinen ,&nbsp;Kati-Sisko Vellonen ,&nbsp;Annette Bauer-Brandl ,&nbsp;Poul Nielsen ,&nbsp;Jarkko Rautio ,&nbsp;Martin Brandl","doi":"10.1016/j.ejps.2025.107397","DOIUrl":"10.1016/j.ejps.2025.107397","url":null,"abstract":"<div><div>Sorafenib is a multi-kinase inhibitor approved for several cancers with poor aqueous solubility, resulting in low oral bioavailability (38–49 %) despite its high permeability. As a BCS Class II compound, its absorption is solubility-/dissolution-limited. Prodrug strategies, such as phosphate esterification, can improve solubility and promote oral bioavailability upon enzymatic cleavage by intestinal alkaline phosphatase (IALP), abundantly expressed at the intestinal brush border membrane and present in the intestinal lumen. This cleavage is hypothesized to lead to a transient supersaturation of the parent drug, enhancing absorption unless (premature) precipitation prevails. Besides traditional in vitro models like Caco-2 cells, recently microdialysis-sampling has been introduced to study ALP-mediated biomimetic conversion of oral phosphate prodrugs in vitro. Microdialysis enables real-time, non-destructive sampling of molecularly dissolved drug, which allows to study the complex inter-related dynamics under (simulated) human gastrointestinal conditions.</div><div>In this study, a novel and new phosphate prodrug of sorafenib (fossorafenib) was synthesized and its physico-chemical and biopharmaceutical properties were evaluated. Fossorafenib exhibited ∼600-fold higher aqueous solubility than sorafenib in HBSS pH 7.4 and was rapidly cleaved by externally added alkaline phosphatase (ALP), yielding supersaturated sorafenib. Combined cleavage &amp; permeability studies across Caco-2 cell monolayers demonstrated rapid bioconversion of fossorafenib in the apical compartment, with permeation of both the converted parent drug but, surprisingly, also the prodrug. Microdialysis enabled real-time monitoring of the biomimetic conversion of fossorafenib without the requirement for enzyme inactivation, thereby allowing for unprecedented mechanistic insights into the interplay between micellar solubilization and enzymatic cleavage. Microdialysis results suggest that micellar incorporation of fossorafenib into mixed micelles of bile salts and phospholipids can hinder enzymatic cleavage by intestinal ALP, thereby potentially limiting the extent of prodrug activation in the intestinal environment. Taken together with the unexpected ability of the prodrug to cross biological/biomimetic barriers, these findings suggest that fossorafenib may not follow the conventional behavior of classical phosphate-ester oral prodrugs in vivo, highlighting the need for further investigation into its unique biopharmaceutical profile.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107397"},"PeriodicalIF":4.7,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695903","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":"Enhanced nuclear enrichment of chemotherapeutics by a biomimetic ZIF-8 nanosystem for multidrug-resistant cancer treatment","authors":"Jingyan Hu ,&nbsp;Jieting Wang ,&nbsp;Junyang Zhuang ,&nbsp;Heng Zhu ,&nbsp;Ao Zhou ,&nbsp;Jingyan Jia ,&nbsp;Xueyang Ji ,&nbsp;Yan Zhao ,&nbsp;Luying Yu ,&nbsp;Yu Deng ,&nbsp;Ning Li ,&nbsp;Fang Wang","doi":"10.1016/j.ejps.2025.107396","DOIUrl":"10.1016/j.ejps.2025.107396","url":null,"abstract":"<div><div>The exclusion of chemo-drugs from their target sites, <em>e.g.</em> the nucleus, is a critical factor contributing to the failure of chemotherapy. Nanoparticle-based technology holds promise for specific delivery of chemo-drugs to nucleus. However, limited lysosomal escape, small size of nuclear pores and incapability of direct regulation of drug efflux-related transporters made great challenges for nanoparticles. Here, a zeolitic imidazolate framework-8 (ZIF-8)-based nanosystem was found able to disrupt lysosomes by the pH-responsiveness of ZIF-8 and mediate the nuclear entry of chemotherapeutics through promotion of their passive diffusion, resulting in the decrease of half maximal inhibitory concentration (IC50) by 3.4-fold compared to free drugs. The additional encapsulation of small interfering RNA (siRNA) to specifically silence multidrug resistance gene 1 (MDR1) for reduction of drug efflux further enhanced the chemotherapy of cancer with multidrug resistance (MDR) (IC50 reduced by 5.2-fold compared to free drugs). With a macrophage membrane biosurface coating onto the nanoparticles, targeted and potent synergistic chemo-gene therapy was achieved in mice bearing cancer with MDR. The unique function of promoting chemotherapeutic nuclear accumulation by ZIF-8-based nanoparticles to fight against MDR may deepen our understanding of the nano/bio-interactions and give novel insights into the design of smart bioresponsive nanosystems for advanced therapy.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107396"},"PeriodicalIF":4.7,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687189","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":"Comparative analysis of irradiation technologies on high-density polyethylene (HDPE) for biopharmaceutical applications","authors":"Blanche Krieguer ,&nbsp;Fabien Girard ,&nbsp;Samuel Dorey ,&nbsp;Nathalie Dupuy ,&nbsp;Sylvain R.A. Marque","doi":"10.1016/j.ejps.2025.107394","DOIUrl":"10.1016/j.ejps.2025.107394","url":null,"abstract":"<div><div>The impacts of e-beam and X-ray irradiation on medical-grade high-density polyethylene (HDPE) are compared with that of gamma irradiation to evaluate their potential effects on pharmaceutical applications. An extensive suite of analytical techniques was employed to evaluate the chemical and physical transformations of irradiated HDPE. Key findings indicated that irradiation did not significantly alter the mechanical properties, as tensile strength and elongation at break remained stable across all irradiation types and doses. Thermal analysis via Differential Scanning Calorimetry (DSC) revealed a slight decrease in melting temperature at higher doses, with an equivalent melting temperature peak observed for all three irradiation technologies. Electron Spin Resonance (ESR) detected alkyl and allyl radicals, which decreased over time, showing no significant differences attributable to irradiation type or dose. Colorimetric analysis indicated yellowing in the samples, linked to specific additives. The quantification of methionine oxidized byproducts by High-Performance Liquid Chromatography (HPLC) demonstrated that the oxidation potential was equivalent for the three irradiation technologies for HDPE. The study concluded that there was a lack of significant impact of irradiation technologies on several physical, chemical and mechanical properties of HDPE.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"217 ","pages":"Article 107394"},"PeriodicalIF":4.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676725","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":"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}