International Journal of Pharmaceutics最新文献

{"title":"Targeted hepatic delivery of ezetimibe via red blood cell-coated nanoparticles for the treatment of non-alcoholic fatty liver disease through inflammation modulation","authors":"Ozgur Esim ,&nbsp;Seyma Adatepe ,&nbsp;Okan Ali Aksoy ,&nbsp;Berk Alp Goksel ,&nbsp;Tugba Yilmaz ,&nbsp;Baris Baykal ,&nbsp;Çigdem Yucel ,&nbsp;Sevilay Erdogan Kablan ,&nbsp;Cemil Can Eylem ,&nbsp;Engin Kocak ,&nbsp;Hakan Erdogan ,&nbsp;Cansel Kose Ozkan ,&nbsp;Emirhan Nemutlu ,&nbsp;Ayhan Savaser ,&nbsp;Yalçın Ozkan","doi":"10.1016/j.ijpharm.2025.126241","DOIUrl":"10.1016/j.ijpharm.2025.126241","url":null,"abstract":"<div><div>This study investigates the potential of red blood cell (RBC) membrane-coated, ezetimibe-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles for targeted therapy of non-alcoholic fatty liver disease (NAFLD). PLGA nanoparticles were fabricated and subsequently camouflaged with RBC membranes to enhance hepatic targeting. The nanoparticles were characterized for size, surface potential, and encapsulation efficiency. Physicochemical characterization revealed increased particle size upon membrane coating (PLGA: 221.2 ± 26.0 nm; RBC-PLGA: 255.2 ± 14.1 nm), corroborated by transmission electron microscopy. In vitro release kinetics were systematically evaluated, showing sustained drug release for both formulations. Biodistribution studies in rats demonstrated predominant hepatic accumulation of both nanoparticles, with higher liver deposition observed for RBC-PLGA (106.43 ± 40.08 µg) compared to uncoated PLGA nanoparticles (101.41 ± 34.15 µg). In vivo efficacy was assessed in a high-fat diet-induced NAFLD rat model. All ezetimibe-treated groups exhibited significant reductions in serum cholesterol levels, hepatic lipid accumulation, and liver enzyme activities. Metabolomics and lipidomics analyses further revealed that RBC-PLGA nanoparticles induced the most pronounced alterations in hepatic metabolic and lipid profiles. Moreover, studies demonstrated route-dependent modulation of key proteins implicated in NAFLD pathogenesis. Collectively, these findings suggest that RBC membrane-coated nanoparticles significantly enhance the liver-specific delivery and therapeutic efficacy of ezetimibe in NAFLD, while offering mechanistic insights into metabolic and lipidomic modulation associated with different administration routes.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"685 ","pages":"Article 126241"},"PeriodicalIF":5.2,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238697","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":"Bio-fabrication of fibrotic liver microtissues as a scalable and drug-responsive in vitro model","authors":"Fatemeh Majidi ,&nbsp;Mahmoud Alipour Choshali ,&nbsp;Amin Izadi ,&nbsp;Mohammad Amin Hajari ,&nbsp;Mona Saheli ,&nbsp;Seyed Ali Ziai ,&nbsp;Massoud Vosough ,&nbsp;Abbas Piryaei","doi":"10.1016/j.ijpharm.2025.126242","DOIUrl":"10.1016/j.ijpharm.2025.126242","url":null,"abstract":"<div><div>Around one-third of the global population is affected by chronic liver diseases which can eventually lead to liver fibrosis. Despite the widespread prevalence and severity of liver fibrosis, only one FDA-approved drug has been introduced so far, possibly due to the lack of a suitable model for pharmacological studies. Today, biomimetic <em>in vitro</em> models are more commonly used compared to <em>in vivo</em> models to avoid ethical concerns and physiological and genetic differences between animals and humans. An effective <em>in vitro</em> model should incorporate human cells, closely mimic <em>in vivo</em> conditions, be reproducible and scalable, and cost-effective. In this study, we developed liver microtissues consisting of available replacement for four major liver cell types encapsulated into a hydrogel containing liver extracellular matrix and alginate using a pneumatic system. To induce fibrosis, the microtissues were exposed to free fatty acids for 21 days. The successful fibrosis induction was confirmed through the evaluation of fibrotic markers at both the molecular and protein levels. To investigate the potential of the generated fibrotic microtissues (FMT) for pharmacological studies, Pioglitazone treatment was performed. Our findings indicated that in response to Pioglitazone, most of the evaluated fibrosis indices in the FMTs modulated and restored the range of control microtissues. Overall, it could be concluding that this model could be used for drug screening and could be a potential platform for precision medicine.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"685 ","pages":"Article 126242"},"PeriodicalIF":5.2,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238627","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":"Self-assembled leuprolide-oleic acid nanoparticles encapsulating docetaxel for synergistic drug delivery","authors":"Jeongro Lee ,&nbsp;Hy Dinh Nguyen ,&nbsp;Sura Saad Abdullah ,&nbsp;Raimar Löbenberg ,&nbsp;Beom-Jin Lee","doi":"10.1016/j.ijpharm.2025.126235","DOIUrl":"10.1016/j.ijpharm.2025.126235","url":null,"abstract":"<div><div>In the present study, an amphiphilic leuprolide acetate (LEU)-oleic acid (OA) conjugate (LOC) was synthesized by conjugating the peptide drug LEU with OA to form self-assembled nanoparticles (LON). This may maximize the synergistic effectiveness of fatty acids and anticancer drugs in prostate cancer. Docetaxel (DTX)-encapsulating LON (LOND) have also been developed for triple-synergistic drug delivery. LON and LOND retained a uniformly spherical morphology and had particle sizes ranging 130.6–159.1 ± 3.1 nm, depending on the freeze drying or redispersion process. Neither LON nor encapsulation of DTX into LON altered the structural behavior of LEU circular dichroism (CD). The nanoparticles were also stable in terms of particle size and polydispersity index (PDI) during storage. LOND exhibited excellent membrane permeability using a Franz diffusion cell. In addition, high lymphatic uptake was observed using an Intralipid®-based absorption assay. LEU and DTX from LON or LOND were released in a controlled manner for 7 d. Notably, the esterase (5 U/mL) significantly decreased the release of LEU, DTX, and LOC. As LOC from LON was enzymatically cleaved, a higher release rate of LEU was achieved. In contrast, a higher release rate of DTX but a lower LEU from LOND was achieved by losing the nanoparticle structure. In a cytotoxicity assay, LOND exhibited significantly higher cytotoxicity against PC3 human prostate cancer cells than LEU or DTX alone, whereas no significant cytotoxicity was observed in normal human foreskin fibroblast (HFF-1) cells. Furthermore, confocal microscopy confirmed the cellular uptake of the nanoparticles in both PC-3 and RAW 264.7 macrophage cells. Based on these findings, LOND, simultaneously releasing LEU, DTX, and fatty acids (such as OA), provides a promising drug delivery platform for triple synergy in the treatment of prostate cancer.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"685 ","pages":"Article 126235"},"PeriodicalIF":5.2,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238665","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":"Functional and morphological characterisation of human colonoid-derived monolayers under inflammatory conditions","authors":"Inês A. Parente ,&nbsp;Linda Chiara ,&nbsp;Lisa Flammini ,&nbsp;Martina Viglioli ,&nbsp;Federica Vacondio ,&nbsp;Federica Gaiani ,&nbsp;Gian Luigi de’Angelis ,&nbsp;Marco Pagano Mariano ,&nbsp;Silvia La Monica ,&nbsp;Elisabetta Barocelli ,&nbsp;Simona Bertoni","doi":"10.1016/j.ijpharm.2025.126228","DOIUrl":"10.1016/j.ijpharm.2025.126228","url":null,"abstract":"<div><div>Despite progress in the diagnosis and treatment of inflammatory bowel disease (IBD), its incidence and prevalence continue to rise. The lack of human preclinical models limits the ability to study disease mechanisms and develop effective therapies. Human colonoids provide a physiologically relevant <em>in vitro</em> system that closely mimics the colonic epithelium. In this study, we established an <em>in vitro</em> IBD model using colonoid-derived monolayers and induced inflammation through exposure to TNF-α and IFN-γ. This treatment significantly impaired epithelial barrier integrity and increased the secretion of inflammatory mediators, like IL-8 and CCL20. Although cell metabolic activity was largely preserved, a cytotoxic effect was observed: the increased apoptosis, revealed also by confocal microscopy, and a compromised epithelial renewal, suggested by lower <em>LGR5</em> mRNA transcription, were evidenced. Functionally, inflammatory conditions led to a significant increase in the paracellular transport of atenolol, while the transport of propranolol remained unaffected, highlighting the impact of intestinal inflammation on oral drug absorption and bioavailability. This model provides a robust platform for studying IBD-related epithelial dysfunctions and evaluating potential therapeutic interventions.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"685 ","pages":"Article 126228"},"PeriodicalIF":5.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218092","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":"Optimisation of Levofloxacin-loaded electrospun fibres for diabetic wound treatment","authors":"Shangjie Lian ,&nbsp;Isabella Dalessio ,&nbsp;Min Zhao ,&nbsp;Luca Casettari ,&nbsp;Dimitrios A. Lamprou","doi":"10.1016/j.ijpharm.2025.126253","DOIUrl":"10.1016/j.ijpharm.2025.126253","url":null,"abstract":"<div><div>Foot ulcers are a common and serious diabetes complication, significantly affecting patients’ quality of life. Chronic diabetic wounds are difficult to treat and often resist conventional therapies. Recently, materials developed through emerging techniques have gained attention for use in wound care and tissue regeneration. This study explores the development of nanofibres through electrospinning to create therapeutic patches for diabetic foot ulcers. Electrospinning allows control over fibres composition, orientation, and diameter, offering advantages such as simplicity and adaptability. Key process parameters, including flow rate, applied voltage, and polymer concentration, were optimized to produce defect-free fibres. The antibiotic levofloxacin was encapsulated in the fibres to assess its controlled release profile. Additionally, blends of chitosan and polycaprolactone (PCL) in various solvent systems were studied to enhance fibre characteristics. The combination leverages the elasticity, mechanical strength, biocompatibility, and versatility of PCL. The resulting composite fibres had an optimal diameter of 400 nm. Drug release analysis showed an initial peak-crucial for antibacterial efficacy-followed by a slower, sustained release phase. This biphasic release is beneficial in preventing infection while supporting prolonged therapeutic action. The findings demonstrate that a carefully designed formulation strategy can optimize fibres performance, making electrospun nanofibers patch a promising tool in the treatment of diabetic foot ulcers.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"685 ","pages":"Article 126253"},"PeriodicalIF":5.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232560","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":"Rational design of immunogenic nanoparticles as a platform to reduce ovarian tumor burden in mice","authors":"Lien Tang ,&nbsp;Ben Marwedel ,&nbsp;Caleb Dang ,&nbsp;Marian Olewine ,&nbsp;Melanie Jun ,&nbsp;Paulina Naydenkov ,&nbsp;Lorél Y. Medina ,&nbsp;Veronica Gayoso ,&nbsp;Ngoc Doan ,&nbsp;Shamus L. O’Leary ,&nbsp;Carmine Schiavone ,&nbsp;Joseph Cave ,&nbsp;Aarush Tutiki ,&nbsp;Tamara Howard ,&nbsp;John D. Watt ,&nbsp;Prashant Dogra ,&nbsp;Rita E. Serda ,&nbsp;Achraf Noureddine","doi":"10.1016/j.ijpharm.2025.126251","DOIUrl":"10.1016/j.ijpharm.2025.126251","url":null,"abstract":"<div><div>Ovarian cancer immunotherapy remains a challenge based on the “cold” tumor microenvironment. Herein we present a rational design to create immunogenic nanoparticles as a multi-agent platform that promotes immune response in a mouse model of ovarian cancer. The hybrid lipid-silica nanosystem is capable of co-loading four types of cargo molecules including a model antigen, nucleic acid-based adjuvant cytosine-p-linked to guanine (CpG, TLR3/9 agonist), glycolipid-based adjuvant monophosphoryl lipid A (MPL, TLR4 agonist) integrated into the lipid coat. The optimization of the nanoplatform in terms of lipid composition, functionalized silica dendritic core formation, and final charge, as well as their compatibility with the complex loading profile highlights an opportunity for enhanced survival of mice with advanced ovarian cancer compared to monotherapy. The inclusion of CpG in the nanoparticle formulation enhanced the survival of mice with ovarian cancer. To interpret these outcomes and guide future design, we also developed a mathematical model of nanoparticle-driven immune activation, which quantified treatment efficacy and identified key parameters governing tumor response. The presented hybrid nanoparticle is tunable, enabling delivery of alternative molecules therefore, thereby highlighting a promising platform for the treatment of peritoneal cancers.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"685 ","pages":"Article 126251"},"PeriodicalIF":5.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232558","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":"Programmable delayed-release container system (PDRCS) for chronotherapeutic delivery: application in personalized treatment for Addison’s disease","authors":"Ahmed Wadi ,&nbsp;Prashant Pandey ,&nbsp;Taha Sheikh ,&nbsp;Rasha Elkanayati ,&nbsp;Achref Cherif ,&nbsp;Jaidev Chakka ,&nbsp;Mohammed Maniruzzaman","doi":"10.1016/j.ijpharm.2025.126245","DOIUrl":"10.1016/j.ijpharm.2025.126245","url":null,"abstract":"<div><div>Chronopharmaceutical systems aim to synchronize drug release with the body’s biological rhythms to enhance therapeutic efficacy and minimize side effects. Current oral delivery technologies largely depend on coating technologies and pH-sensitive polymers, which are limited by significant inter- and intra-patient variability, as well as technical constraints in coating reproducibility. To address these challenges, we present a novel 3D-printed Programmable Delayed-Release Container System (PDRCS) for pH-independent, time-specific pulsatile drug delivery. Hydrocortisone was selected as the model drug to demonstrate chronotherapeutic targeting for primary adrenal insufficiency (Addison’s disease). The system consists of an ethyl cellulose shell manufactured via fused deposition modeling (FDM), encapsulating a layered core comprising a swelling hydrogel disc, a separating barrier, and an immediate-release hydrocortisone tablet. Upon immersion in dissolution media, water enters through engineered perforations, triggering the swelling disc to expand and build internal pressure until rupture of the shell occurs, resulting in drug release. By adjusting perforation diameters 1.0, 1.5, and 2.0 mm, lag times of 28, 20, and 12 h, respectively, were achieved. <em>In vitro</em> studies confirmed the system’s pH-independent behavior. Solid-state characterization (PXRD, FTIR, DSC, TGA) validated formulation stability, processing integrity, and revealing an increase in crystallinity after extrusion followed by reduction upon 3D printing. SEM imaging, rupture force analysis, and hydrogel swelling test were conducted to characterize the rupture behavior. This mechanically governed, rupture-based delivery platform enables customizable and reliable time-controlled oral drug administration, supporting personalized chronotherapeutic regimens.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"685 ","pages":"Article 126245"},"PeriodicalIF":5.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228486","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":"Power and fluid stress in disposable square stirred tank to streamline pharmaceutical process development","authors":"Matteo Antognoli ,&nbsp;Hessam Qeysari ,&nbsp;Federico Alberini ,&nbsp;Alessandro Paglianti ,&nbsp;Pushpinder Singh ,&nbsp;Andrea Albano","doi":"10.1016/j.ijpharm.2025.126243","DOIUrl":"10.1016/j.ijpharm.2025.126243","url":null,"abstract":"<div><div>Single-use systems have quickly become a standard in biopharmaceutical manufacturing due to their superior operational efficiency, flexibility and cost-effectiveness. Despite their recent and intensive use, disposable stirred tanks are not fully understood and require further characterization. Single-use square stirred tanks may exhibit unusual power consumption that may impact drug substances and drug product critical quality attributes. In this work, we use torque measurements and particle image velocimetry to validate a Computational Fluid Dynamics model designed to elucidate the fluid dynamics in a transparent replica of the Flexel® LevMixer® 50 L. Using the validated model and exploiting the renormalization group k-ε two filling-volume-dependent behaviors were identified: (i) the Swirling flow regime, characterized by low power consumption per unit volume, and (ii) the Engulfed flow regime, which requires significantly higher power. For both regimes, fluid stress induced by the mechanical agitation from the impeller is thoroughly analyzed for intensity and frequency. A strong correlation between fluid stress and power consumption is demonstrated, with implications for pharmaceutical process development involving stress-sensitive drug substances and products. These findings, which correlate power consumption with fluid stress, can streamline drug development in the pharmaceutical industry and potentially support future development of new process analytical technologies to better control drug substance and drug product quality attributes.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"685 ","pages":"Article 126243"},"PeriodicalIF":5.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225391","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":"Harnessing nanotechnology for improved drug delivery across the blood-brain barrier and enhanced neural repair","authors":"Miaomiao Xu,&nbsp;Heng Wang,&nbsp;Chengchen Wang,&nbsp;Chu Wang,&nbsp;Shenghao Hu,&nbsp;Lixing Weng","doi":"10.1016/j.ijpharm.2025.126221","DOIUrl":"10.1016/j.ijpharm.2025.126221","url":null,"abstract":"<div><div>The blood–brain barrier (BBB) serves as the primary interface between the bloodstream and the brain, maintaining the delicate balance and homeostasis crucial for the proper functioning of the central nervous system (CNS). However, the BBB’s selective permeability poses significant challenges for drug delivery, hindering the treatment of CNS-related diseases. In recent years, advancements in technology have revolutionized approaches to drug delivery across the BBB, yet few nanomaterials have achieved success in clinical trials. In this review, we first examine the structure and function of the BBB, followed by an analysis of the mechanisms by how drugs can penetrate it. We then focus on strategies that leverage nanomaterials to facilitate BBB crossing, categorizing these materials based on their compositions. Additionally, we specifically highlight recent advances in the development of nanomedicines from nanomaterials for the treatment of various CNS diseases and summarize nanomaterials that have been tested in clinical trials for nerve repair. Finally, we provide a perspective on future directions in this field.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"685 ","pages":"Article 126221"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212667","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":"Multifunctional nanozyme-embedded hydrogels for advanced diabetic wound management","authors":"Yanyu E,&nbsp;Jiuhong Zhao,&nbsp;Wenjing Zhu,&nbsp;Guixia Ling,&nbsp;Peng Zhang","doi":"10.1016/j.ijpharm.2025.126220","DOIUrl":"10.1016/j.ijpharm.2025.126220","url":null,"abstract":"<div><div>Diabetes mellitus imposes a substantial global healthcare burden due to its chronic progression and associated complications. Diabetic wound healing is severely compromised by hyperglycemia-induced pathological alterations, including osmotic imbalance, bacterial proliferation, and impaired tissue regeneration. Critically, excessive reactive oxygen species (ROS) in the wound microenvironment perpetuate inflammation, degrade extracellular matrix (ECM), and delay healing, necessitating advanced therapeutic dressings. Hydrogels emerge as ideal candidates owing to their high hydration capacity, biocompatibility, and structural mimicry of native ECM. Nanozymes (NZs)—nanomaterials with enzyme-mimetic catalytic activities (e.g., superoxide dismutase, catalase)—offer superior stability and catalytic efficiency compared to natural enzymes. Integrating NZs into hydrogels yields multifunctional nanozyme-embedded hydrogels (NZ@hydrogels) that synergistically combine ROS scavenging, antimicrobial action, and pro-healing functions. This review systematically analyzes diverse NZ@hydrogel systems leveraging enzymatic mechanisms (e.g., glucose oxidase-like, peroxidase-like activities) for diabetic wound therapy, emphasizing their roles in modulating inflammatory responses, hypoxia alleviation, and angiogenesis promotion. Current translational challenges, including biocompatibility optimization, long-term biosafety assessment, and scalable manufacturing, are critically evaluated. Future perspectives focus on accelerating clinical adoption through advanced material design and rigorous preclinical validation, aiming to stimulate transformative research in precision wound management.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"685 ","pages":"Article 126220"},"PeriodicalIF":5.2,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212699","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}