International Journal of Pharmaceutics: X最新文献

{"title":"Corrigendum to \"Preparation of colon-targeted pellets loaded with filgotinib/berberine hydrochloride and Their application in ulcerative colitis therapy\" [International Journal of Pharmaceutics: X 2025 (10) 100415].","authors":"Jinglong Wang, Zhixuan Kuang, Binglian Chen, Chenxi Yan, Bowen Shi, Guofei Li","doi":"10.1016/j.ijpx.2025.100471","DOIUrl":"https://doi.org/10.1016/j.ijpx.2025.100471","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.ijpx.2025.100415.].</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"11 ","pages":"100471"},"PeriodicalIF":7.9,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13282638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-assembling rose-derived nanovesicles: A multifunctional tool for tissue regeneration.","authors":"Antonella Barone, Luigi Ciriolo, Salvatore Panza, Nicola d'Avanzo, Giuliana Faggio, Giacomo Messina, Tanzeel U Rehman, Caterina M Tone, Maria P De Santo, Rosario Mare, Anna M Tolomeo, Massimo Fresta, Donatella Paolino","doi":"10.1016/j.ijpx.2025.100465","DOIUrl":"10.1016/j.ijpx.2025.100465","url":null,"abstract":"<p><p>The development of biocompatible nanotherapeutics for skin regeneration remains a major goal in regenerative medicine. Here, we report the isolation and characterization of rose petal-derived extracellular vesicle-like nanovesicles (RPDNVs) obtained by differential ultracentrifugation and size exclusion chromatography. Comprehensive physicochemical analyses confirmed their vesicular morphology, nanoscale size distribution, and antioxidant-enriched molecular cargo, including lipids, phenols, and proteins. RPDNVs demonstrated mechanical stability compatible with tissue interfacing. Functionally, they enhanced fibroblast migration and modulated extracellular matrix gene expression without inducing fibrotic responses. Their biocompatibility was confirmed by in vitro and in vivo studies on human volunteers, thus supporting their translational relevance. Notably, RPDNVs retained structural and functional stability following freeze-drying in the absence of cryoprotectants, enabling long-term storage. These results establish RPDNVs as a promising class of plant-derived nanocarriers for therapeutic skin repair.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"100465"},"PeriodicalIF":7.9,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12741408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multifunctional fungal defensin bladesin loaded-hydrogel for accelerated infectious wound healing.","authors":"Yating Chen, Yan Yu, Bingzheng Shen","doi":"10.1016/j.ijpx.2025.100463","DOIUrl":"10.1016/j.ijpx.2025.100463","url":null,"abstract":"<p><p>Wound management is significantly challenged by drug-resistant bacterial infections. In this study, a novel fungal defensin peptide derived from <i>Blastomyces dermatitis</i> was identified. The full-length peptide named bladesin was composed of 116 amino acids containing three regions: signal peptide, pro-peptide, and mature peptide. Sequence and structural analysis revealed that the linear mature peptide (reduced type) was consisted of 38 amino acids. The mature bladesin contains three intramolecular disulfide bonds (Cys4-Cys29, Cys14-Cys35 and Cys18-Cys37) and can form a characteristic cysteine-stabilized alpha-beta motif in the native state. <i>In vitro</i> studies demonstrated it exhibited potent antibacterial activity against Gram-positive pathogens with minimum inhibitory concentrations (MICs) ranging from 4 to 32 μM. Furthermore, bladesin was found to promote the proliferation of NIH/3 T3 fibroblasts cells. Using the Poloxamer 407 as the thermosensitive matrix, a bladesin-loaded sustained-release hydrogel was successfully prepared. <i>In vivo</i> experiments showed bladesin hydrogels can accelerate cutaneous wound healing. The mechanism exploration revealed that it can promote pathogen clearance, enhance collagen deposition and regulate inflammatory responses. These findings suggested that this bladesin-based dressings represented a promising therapeutic strategy for the treatment of infected wounds.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"100463"},"PeriodicalIF":7.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12723373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dextran-modified dissolving microneedle patches for effective amelioration of psoriasis through transdermal delivery of hesperidin.","authors":"Nooshin Etemadi, Jaleh Varshosaz, Nahal Shamaeizadeh, Amir Mohamadsharifi Renani, Mohsen Minaiyan","doi":"10.1016/j.ijpx.2025.100462","DOIUrl":"10.1016/j.ijpx.2025.100462","url":null,"abstract":"<p><p>Psoriasis is a chronic, multifactorial, proliferative inflammatory skin disease characterized by immune-mediated relapsing and remitting phases. Topical treatments for mild to moderate psoriasis, as well as systemic treatments for severe cases, can be insufficiently effective and are often associated with significant side effects. The primary objective of this study was to develop a dissolvable microneedle patch containing the flavonoid hesperidin within a polymeric matrix composed of dextran modified polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) aiming to achieve effective control of psoriasis symptoms. The innovative laser ablation technique used in master mold fabrication resulted in well-structured pyramidal arrays, as evidenced by SEM images of the microneedle patches (MNPs). Various formulations were developed in which almost complete dissolving of the needle occured only 30 s. MNP containing PVP 150 mg, PVA 75 mg and Dextran 50 mg, with the highest compressive failure force, was able to sink into the skin well. Over 70 % of hesperidin was released within approximately 15 h from the dissolved MNs into skin. Animal studies were conducted using an imiquimod-induced psoriasis mouse model. PASI score or cumulative amount of three parameters; desquamation or scaling, erythema, and induration or thickness for each group on experimental days 1 to 7 were studied. Significant clinical improvement on PASI scores, was observed in the group treated with hesperidin-loaded optimal MNP (1.67 ± 0.47) compared to the positive control (11.67 ± 0.47) and the oral hesperidin groups (6.00 ± 0.82). The results of this study indicate that dextran modified MNPs of hesperidin can reduce epidermal hyperplasia and inflammatory cell infiltration, demonstrating an effective method for transdermal drug delivery.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"100462"},"PeriodicalIF":7.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12720357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of the conjugation manner of targeting agent and tandem cell-penetrating peptide on the efficacy of mitomycin C liposomes in treating triple-negative breast tumors.","authors":"Mehrnaz Salahi, Jaleh Varshosaz, Mahboubeh Rostami, Salar Nasr Esfahani, Arsham Hekmat, Ali Jahanian-Najafaabadi, Mohsen Minayian","doi":"10.1016/j.ijpx.2025.100457","DOIUrl":"10.1016/j.ijpx.2025.100457","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) remains one of the most aggressive subtypes with limited therapeutic options. To address this unmet need, this study aimed to enhance the cellular uptake and cytotoxicity of mitomycin C (MMC) using surface-modified nanoliposomes functionalized with poly-L-arginine (PLA), a cell-penetrating peptide, and chondroitin sulfate (CS), a CD44-targeting ligand. Another object was to investigate how the conjugation manner of the targeting agent-chondroitin sulfate (CS), a CD44-targeting ligand, and a tandem cell-penetrating peptide (CPP) made of poly-L-arginine (PLA)-affects the enhancement of cellular uptake and anti-tumor effects of Mitomycin C (MMC) nanoliposomes in triple-negative breast cancer (TNBC). We synthesized and characterized four liposomal formulations; CS-liposomes, PLA-liposomes, PLA-CS-liposomes, and CS-PLA-liposomes and their particle size, polydispersity index, zeta potential, encapsulation efficiency, and drug release were evaluated. In vitro studies on 4 T1 TNBC cells included cytotoxicity (MTT), cellular uptake, apoptosis, cell cycle arrest, and caspase-3/8 expression (qRT-PCR). In vivo efficacy was tested in BALB/c mice bearing orthotopic 4 T1 tumors by monitoring tumor growth, body weight, and histopathology (H&E and Ki-67). Optimized PLA-CS liposomes had a mean particle size of 144.0 ± 2.4 nm, a PDI of 0.31 ± 0.02, and 73 % encapsulation efficiency, with sustained MMC release over 24 h. PLA-functionalized liposomes showed significantly greater cytotoxicity and uptake than free MMC and non-targeted controls. They induced G1 cell cycle arrest and strongly upregulated caspase-3 (+64-fold in CS-PLA, +13-fold in PLA-CS), consistent with activation of the intrinsic apoptosis pathway. Animal studies revealed PLA-CS liposomes produced the strongest tumor suppression (Ki-67 index 6 %), reduced tumor grade to 1, and showed no liver or kidney metastasis. All liposomal formulations performed better than free MMC in tumor control and safety. PLA-CS-liposomes provide a potent and well-tolerated delivery platform for MMC in TNBC, combining improved tumor targeting, enhanced apoptotic response, and favorable organ safety.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"100457"},"PeriodicalIF":7.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12753249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145878347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal pharmacokinetic and safety studies of an antibody-erythropoietin fusion protein for Alzheimer's disease.","authors":"Rudy Chang, Devaraj V Chandrashekar, G Chuli Roules, Nataraj Jagadeesan, Emi Iwasaki, Adenike Oyegbesan, Hayk Davtyan, Rachita K Sumbria","doi":"10.1016/j.ijpx.2025.100459","DOIUrl":"10.1016/j.ijpx.2025.100459","url":null,"abstract":"<p><p>Erythropoietin (EPO) shows promise for Alzheimer's disease (AD) but has poor brain penetration, necessitating high doses that cause hematopoietic side effects. To improve brain delivery, EPO was fused to a transferrin receptor monoclonal antibody (TfRMAb), and this study evaluated the pharmacokinetics (PK), safety, and efficacy of repeated TfRMAb-EPO dosing in mice to further its preclinical development. C57BL/6J male mice (10 weeks old, <i>n</i> = 4-5/dose) received subcutaneous (SQ) low (1 mg/kg), mid (3 and 6 mg/kg), or high (20 mg/kg) TfRMAb-EPO doses for 4 weeks. The 1 mg/kg dose showed no adverse effects and resulted in sustained brain and plasma exposure, making it suitable for longitudinal dosing. Paradoxically, higher doses reduced plasma and brain exposure, and altered hematocrit, TfR expression, and spleen weight; these changes were largely reversible. Anti-drug antibodies and TfR expression changes likely contributed to reduced plasma exposure at higher doses. Subsequently, 5.5-month-old APP_SAA knock-in (KI) mice (<i>n</i> = 6) received 1 mg/kg TfRMAb-EPO SQ for 14 weeks. Controls included vehicle-treated APP_SAA KI and APP wild-type mice (<i>n</i> = 4-5/group). Despite the low dose, TfRMAb-EPO showed profound brain Aβ-lowering effects measured by immunostaining (70-80 % reduction, <i>p</i> < 0.001) and improved spatial memory in the Y maze (<i>p</i> < 0.05). These findings offer important preclinical data to guide dose optimization in longitudinal studies using TfRMAb-based therapeutics, specifically TfRMAb-EPO, given the movement of TfRMAb-based therapeutics into clinical trials for AD, and show the robust therapeutic potential of low-dose TfRMAb-EPO in APP_SAA KI AD mice.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"100459"},"PeriodicalIF":7.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12765438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel hybrid tri-polymer hyalurosomes: unlocking next-generation trans-tympanic therapeutics through multi-Scale evaluations","authors":"Sadek Ahmed ,&nbsp;Heba Attia ,&nbsp;Osama Saher","doi":"10.1016/j.ijpx.2025.100425","DOIUrl":"10.1016/j.ijpx.2025.100425","url":null,"abstract":"<div><div>Acute otitis media (AOM) remains one of the most common middle ear infections, particularly in children, necessitating advanced non-invasive therapeutic strategies. This study introduces Novel Hybrid Tri-Polymer Hyalurosomes, an innovative vesicular system designed to enhance trans-tympanic delivery of ciprofloxacin (CFX). The nanosystems were fabricated using the ethanol injection technique and optimized via a 2³ factorial design, evaluating the effects of hyaluronic acid (HA): drug ratio (Factor-A), surfactant: HA ratio (Factor-B), and L121: Brij L4 ratio (Factor-C) on critical quality attributes. The optimized formula, selected using a high desirability index (0.996), exhibited high entrapment efficiency (EE%) of 90.28 %, small particle size (PS) of 218.15 nm, and promising zeta potential (ZP) of −40.4 mV. Transmission electron microscopy (TEM) confirmed the uniform spherical morphology of the optimized formula, which also exhibited a characteristic bi-phasic sustained release profile and pseudoplastic rheological behavior, enhancing ease of application and retention at the administration site. Moreover, the formulation demonstrated excellent storage stability and markedly improved mucoadhesive properties. Ex vivo permeation studies revealed a 2.53-fold enhancement ratio compared to CFX solution. Microbiological assessments showed significantly lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against <em>Pseudomonas aeruginosa</em> and <em>Staphylococcus aureus</em>, along with superior biofilm inhibition activity. Confocal laser scanning microscopy (CLSM) confirmed deeper tissue penetration, consistent with the permeation findings. Additionally, in vivo histopathological evaluation demonstrated the safety of the optimized formula with no observable tissue irritation or damage. Collectively, Novel Hybrid Tri-Polymer Hyalurosomes present a promising non-invasive trans-tympanic delivery platform, holding significant potential for advancing AOM therapy.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100425"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Foamable pluroleosomes system loaded with amlodipine as a repurposed antibacterial topical formulation against MRSA-induced infection; optimization, in-vitro, ex-vivo, and in-vivo studies","authors":"Alaa S. Eita ,&nbsp;Amna M.A. Makky ,&nbsp;Asem Anter ,&nbsp;Islam A. Khalil","doi":"10.1016/j.ijpx.2025.100406","DOIUrl":"10.1016/j.ijpx.2025.100406","url":null,"abstract":"<div><div>Amlodipine besylate (AML) is a renowned antihypertensive drug currently acknowledged for having antibacterial activity. AML repositioning can be helpful in the defeat of microbial-resistant strains. Loading amlodipine in the pluroleosomes (PLOs) foam system is desired to approach innovative remedies with a convenient application capable of targeting deep infections. The mixture design was employed to generate different pluroleosomes formulations consisting of various ratios of Pluronic F-127, oleic acid, and soya lecithin loaded with amlodipine. Based on the desirability function, the selected optimized formula (AML-PLOs), consisting of 4.875 for lecithin, one for oleic acid, and 1.125 for pluronic, exhibits a particle size of 320.56 ± 15.5 nm, a polydispersity index of 0.4461 ± 0.03, a surface charge of 15.261 ± 0.62 mV, and AML entrapment of 71.25 ± 3.52 %. The morphological image displayed a uniform spherical shape at the nanoscale. In addition, thermal analysis and infrared spectroscopy (IR) proved the suitability of AML-pluroleosome vesicles. Tween 20, the selected nonionic surfactant in foam preparation, achieved the demand values of foam parameters and showed adequate stability upon storage for up to 90 days. The selected AML-PLO foam showed complete AML release after 48 h in a controlled manner, and the cumulative amount permeated after 24 h was about 45 %. Efficient penetration through dermal strata was affirmed by utilizing a confocal microscope. <em>In vitro</em> microbiological assay, besides the <em>in vivo</em> microbiological and histopathological studies employing a wound healing model, validated the antibacterial efficacy of amlodipine. Those outcomes demonstrated that the prepared pluroleosome foam system of AML is a competent candidate for combating topical bacterial infection.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100406"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking hypoxic barrier: Oxygen-supplied nanomaterials for enhanced T cell-mediated tumor immunotherapy","authors":"Shuo Xiang ,&nbsp;Hui Zhan ,&nbsp;Jimin Zhan ,&nbsp;Xin Li ,&nbsp;Xiaoji Lin ,&nbsp;Wenjie Sun","doi":"10.1016/j.ijpx.2025.100400","DOIUrl":"10.1016/j.ijpx.2025.100400","url":null,"abstract":"<div><div>Hypoxia in the tumor microenvironment (TME) is a critical barrier to effective cancer immunotherapy, as it suppresses T cell infiltration and response while fostering immune evasion. Oxygen-supplied nanomaterials (OSNs) have recently emerged as promising tools to alleviate hypoxia, modulate the TME, and enhance the efficacy of immunotherapies. This review explores the synergistic interplay between OSNs and T lymphocytes in overcoming hypoxia-driven immune suppression. We discuss the mechanisms by which hypoxia limits T cell functionality, infiltration, and cytotoxicity, and highlight how nanomaterials restore oxygenation, boost immune activation, and improve chemokine-mediated T cell recruitment. Key advances in nanotechnology, including perfluorocarbon-based systems and catalytic nanoparticles, are evaluated for their ability to improve anti-tumor immunity and synergize with immune checkpoint inhibitors and chimeric antigen receptor-T cell therapies. Finally, we address the challenges of nanomaterial delivery, safety, and clinical translation, emphasizing opportunities for personalized strategies. OSNs offer transformative potential to enhance T cell-mediated anti-tumor responses, advancing immunotherapy's frontier.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100400"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral delivery of chitosan/hyaluronic-acid-coated milk-derived exosomes for ulcerative-colitis amelioration","authors":"Chao Deng ,&nbsp;Xinyi Cheng ,&nbsp;Qingying Sun ,&nbsp;Yeliaman Yeerbolati ,&nbsp;Rui Zheng ,&nbsp;Youyi Liu ,&nbsp;Ying Yao ,&nbsp;Yanbing Shen ,&nbsp;Kewei Wang ,&nbsp;Jianfeng Huang","doi":"10.1016/j.ijpx.2025.100447","DOIUrl":"10.1016/j.ijpx.2025.100447","url":null,"abstract":"<div><div>Restoring intestinal-barrier homeostasis is crucial in treating ulcerative colitis (UC). Milk-derived exosomes, known for their potent biological properties, hold promise in promoting intestinal-barrier repair. However, their stability and targeting ability during gastrointestinal transit remain challenging. To address this, we engineered exosomes via layer-by-layer (LBL) encapsulation, enhancing their stability, controlled release, and targeted delivery. In a C57BL/6 J mouse model of UC induced by dextran sulfate sodium, oral administration of LBL-encapsulated milk-derived exosomes (LBL-Exos) significantly improved the intestinal barrier, including the physical, mucus, and immune barriers, thereby effectively alleviating the symptoms of UC, even at half the exosome dosage. These effects were also associated with reduced apoptosis and inhibition of the PI3K/AKT signaling pathway. This study demonstrates the therapeutic potential of engineered milk-derived exosomes in UC treatment, offering a promising approach for treating colitis and paving the way for the broader use of natural exosomes in related diseases.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100447"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}