International Journal of Pharmaceutics: X最新文献

{"title":"Biomimetic nanocarriers for the therapy and management of intestinal inflammations","authors":"Rupam Bera ,&nbsp;Shivam Pathak ,&nbsp;Pradhi Srivastava ,&nbsp;Maitrayee Ghosh ,&nbsp;Anjana Sharma ,&nbsp;Noor Zaheer Ahmed ,&nbsp;Ritu Karwasra ,&nbsp;Usama Akram ,&nbsp;Pawan Kumar ,&nbsp;Bhupesh Sharma ,&nbsp;Nitin Sharma","doi":"10.1016/j.ijpx.2025.100377","DOIUrl":"10.1016/j.ijpx.2025.100377","url":null,"abstract":"<div><div>Intestinal inflammation particularly inflammatory bowel disease poses significant clinical challenges due to its chronic nature, limited treatment efficacy and adverse effects of conventional therapies like corticosteroids and biologics. Biomimetic nanocarriers have emerged as a transformative strategy to overcome these limitations by leveraging natural cell membranes for targeted drug delivery. This review critically examines the application of biomimetic nanocarriers as precision therapeutics for intestinal inflammation. We discuss key fabrication techniques including extrusion, sonication and microfluidics used to coat synthetic nanocarriers with membranes derived from several biological sources such as macrophages, neutrophils, platelets, stem cells and bacteria. These biomimetic coatings exploit inherent biological functions such as immune evasion, receptor-mediated binding to inflamed endothelium and responsiveness to inflammatory stimuli. Preclinical studies demonstrate that biomimetic nanocarriers effectively suppress pro-inflammatory pathways like NF-κB, NLRP3, sequester cytokines, promote mucosal healing and restore gut microbiota balance while minimizing systemic toxicity. Despite promising outcomes in animal models, clinical translation faces hurdles in membrane isolation standardization, long-term biosafety, and regulatory alignment. Future advancements require interdisciplinary efforts to optimize pharmacokinetics, enhance tissue-specific targeting, and integrate personalized designs. Biomimetic nanocarriers represent a paradigm shift toward disease-modifying therapies, offering potential for sustained remission in intestinal inflammation management.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100377"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908609","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":"Electrospinning of animal-free derived collagen-like protein: Development and characterization of VECOLLAN®- nanofibers for biomedical applications","authors":"Christoph Krauss ,&nbsp;Maria Montero Mirabet ,&nbsp;Jian-Feng Zhang ,&nbsp;Karsten Mäder","doi":"10.1016/j.ijpx.2025.100398","DOIUrl":"10.1016/j.ijpx.2025.100398","url":null,"abstract":"<div><div>This study investigates the potential of VECOLLAN®, a recombinant, novel, non-animal-derived collagen-like protein, for use in electrospinning applications relevant to biomedical and drug delivery sectors. Given the limitations of animal-derived collagens, including immunogenicity and variability, VECOLLAN® offers a promising alternative due to its biotechnological production and non-immunogenic, non-allergenic, and non-inflammatory properties. We optimized the electrospinning parameters for VECOLLAN® and examined the effects of a novel coaxial crosslinking approach on the dissolution and disintegration behaviors of the resultant fibers. Our results demonstrate that VECOLLAN®-based fibers can achieve varying degrees of water insolubility, influenced by crosslinker concentration and type of crosslinker. Additionally, the fibers exhibit distinct swelling behaviors. With the addition of hyaluronic acid, the water absorption capacity could be increased. We investigated the distribution of silver nanoparticles within the fibers, confirming the homogeneity of the coaxial electrospinning process. Mechanical tests revealed that increased crosslinker concentrations lead to greater stability and rigidity, while elastin incorporation improved elongation properties. This study lays the groundwork for developing electrospun fibers made from a non-animal-derived collagen-like protein, highlighting the potential for applications in drug delivery and tissue engineering. Future research should focus on assessing the biocompatibility of these fibers further to explore their utility as drug carriers or cell scaffolds. Overall, our findings underscore the promising properties of VECOLLAN®-based fibers in advancing innovative solutions in the biomedical and drug delivery sectors.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100398"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154408","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":"Improved bioavailability and anti-nephrotoxicity efficacy of polydatin on cisplatin-induced AKI via a dual-targeting fucoidan delivery system","authors":"Yinghan Wang ,&nbsp;Shichao Liu ,&nbsp;Feikai Zhu ,&nbsp;Xuefei Wang ,&nbsp;Hanyu Wang ,&nbsp;Lin Long ,&nbsp;Jun Xiao ,&nbsp;Chuanlong Guo","doi":"10.1016/j.ijpx.2025.100422","DOIUrl":"10.1016/j.ijpx.2025.100422","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is a common and serious complication in clinical practice, especially when using chemotherapy drug cisplatin, which severely limits its anti-cancer efficacy. This study developed a novel nano delivery system (Fu-4-PBA/Po NPs) that combines fucoidan (Fu), endoplasmic reticulum stress (ERS) inhibitor 4-phenylbutyric acid (4-PBA), and natural antioxidant Polydatin (Po) to simultaneously alleviate cisplatin induced oxidative stress and ERS. The optimized Fu-4-PBA/Po NPs showed an average size of 102 ± 3.46 nm, a zeta potential of −16.5 ± 0.49 mV, and a high drug loading capacity of 10.34 ± 0.6 %. They exhibited excellent stability and a sustained release profile <em>in vitro</em>. <em>In vitro</em> results showed that treatment with Fu-4-PBA/Po NPs led to a marked increase in cell survival by 34.73 ± 3.54 percentage points compared to the model group, which had a survival rate of 45.97 ± 2.76 %. Furthermore, Fu-4-PBA/Po NPs effectively inhibited the accumulation of reactive oxygen species (ROS), mitochondrial membrane potential decline, and calcium ion release by targeting P-selectin and endoplasmic reticulum (ER) at the site of inflammation, and significantly alleviate cisplatin induced cell apoptosis. Mechanism studies showed that nanocomposites alleviate ERS by inhibiting the PERK-eIF2α-ATF4-CHOP pathway, while blocking the activation of the cGAS-STING pathway, thereby reducing DNA damage and inflammatory response. Pharmacokinetic studies showed that the peak concentration (Cmax) of the nanoparticles reached 2.2 times that of free Po, and the area under the curve (AUC) increased by 2 times. In animal studies, administration of Fu-4-PBA/Po NPs at a dose of 100 mg/kg notably ameliorated renal function, as indicated by reductions in serum creatinine (SCr) and blood urea nitrogen (BUN) levels by 84.3 % and 62.4 %, respectively, and also improved kidney histopathology. This study provided a dual targeted nano-delivery strategy for cisplatin induced AKI therapy, which has important clinical application potential.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100422"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358114","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":"Engineered extracellular vesicles demonstrate altered endocytosis and biodistribution and have superior oral siRNA delivery efficiency compared to lipid nanoparticles","authors":"Ning Ding ,&nbsp;Armond Daci ,&nbsp;Vanesa Krasniqi ,&nbsp;Rachel Butler ,&nbsp;Alan Goddard ,&nbsp;Qing Guo ,&nbsp;Yunyue Zhang ,&nbsp;Jizhou Zhong ,&nbsp;K.L. Andrew Chan ,&nbsp;Maya Thanou ,&nbsp;Driton Vllasaliu","doi":"10.1016/j.ijpx.2025.100428","DOIUrl":"10.1016/j.ijpx.2025.100428","url":null,"abstract":"<div><div>Oral administration of RNA therapeutics remains a major unsolved challenge due to currently insurmountable biological barriers. Extracellular vesicles (EVs) are natural carriers capable of traversing the intestinal barrier, but inefficient RNA loading into EVs in general severely limits the application of EVs for RNA delivery. Here, we utilize a microfluidic engineering platform to generate milk-derived EV-lipid nanoparticle (EV-LNP) hybrids for oral delivery of RNA. The process produced uniform nanoparticles (133 nm, polydispersity index 0.19) with &gt;45 % dual-positive fusion efficiency, significantly outperforming freeze–thaw hybridization. Compared to conventional LNPs, EV-LNP hybrids exhibited lower cytotoxicity, altered epithelial uptake pathways, and markedly improved intestinal epithelial transport. Importantly, the hybrids retained gene-silencing efficacy following exposure to simulated intestinal fluids, achieving 40–60 % glyceraldehyde 3-phosphate dehydrogenase knockdown in Caco-2 cells, which was superior to LNPs. Oral gavage in mice revealed preferential colonic accumulation of EV-LNP hybrids compared to native EVs or LNPs, indicating strong potential for local RNA therapy in gut diseases such as colitis. Collectively, this study establishes a scalable, bioinspired delivery platform that addresses key translational barriers for oral RNA therapeutics and enables targeted delivery to the colon.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100428"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462785","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":"Development of 3D printed dexamethasone chewable tablets for prophylaxis of chemotherapy-induced nausea and vomiting in children","authors":"Adrin Dadkhah ,&nbsp;Tobias Gutowski ,&nbsp;Eva-Maria Wansing ,&nbsp;Alexander von Hugo ,&nbsp;Wilhelm Woessmann ,&nbsp;Beate Winkler ,&nbsp;Gefion Franke ,&nbsp;Michael Baehr ,&nbsp;Claudia Langebrake","doi":"10.1016/j.ijpx.2025.100380","DOIUrl":"10.1016/j.ijpx.2025.100380","url":null,"abstract":"<div><div>Dexamethasone (Dexa) is widely used for the prophylaxis of chemotherapy-induced nausea and vomiting. In pediatric patients, individual dosing often requires the manipulation of commercial tablets, leading to dose inaccuracies, higher treatment complexity and poor acceptance due to Dexa's intensely bitter taste.</div><div>This study aimed to develop 3D-printed chewable Dexa tablets with effective taste masking for pediatric oncology. Tablets were produced using semi-solid extrusion (SSE). The impact of excipients on printability and taste masking was evaluated, and the thermal stability of Dexa was assessed using DSC and TGA. Further assessments included disintegration, in vitro dissolution, content and mass uniformity, short-term stability and a sensory evaluation in healthy adult volunteers.</div><div>The tablets demonstrated excellent uniformity of mass (average RSD 0.75 %) and API content (99.35 % ± 2.92 %). Disintegration times ranged from 96 s (2 mg) to 733 s (12 mg). Complete drug release was achieved within 2 h. Thermal analysis showed no degradation of Dexa, and storage stability was confirmed for at least 5 weeks. A substantial reduction in bitterness was observed.</div><div>In conclusion, SSE enabled the reproducible production of child-appropriate, individually dosed Dexa chewable tablets with effective taste masking, supporting their clinical application in pediatric oncology.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100380"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144891999","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":"Does the appearance of the Magenstrasse depend on the amount of water consumed?","authors":"Linus Großmann ,&nbsp;Johanna Cyrus ,&nbsp;Stefan Senekowitsch ,&nbsp;Toni Wildgrube ,&nbsp;Theodora Tzakri ,&nbsp;Marie-Luise Kromrey ,&nbsp;Werner Weitschies ,&nbsp;Michael Grimm","doi":"10.1016/j.ijpx.2025.100365","DOIUrl":"10.1016/j.ijpx.2025.100365","url":null,"abstract":"<div><div>The <em>Magenstrasse</em> (stomach road) is a phenomenon describing the rapid evacuation of water drunken after a solid meal from the stomach. So far, its existence has been demonstrated for water volumes of 150 mL or more. The aim of this three-arm, randomised, cross-over, 12-subject study was to investigate whether the <em>Magenstrasse</em> is also present for smaller water volumes. For this purpose, gastric emptying of 50, 100 or 150 mL of water that was administered after a light meal was determined using MR imaging. With each dose of water, a fast-dissolving compression coated tablet containing caffeine and iron oxide as well as a hard capsule containing stable isotope labelled caffeine and medium-chain triglycerides were administered. This made it possible to determine the initial localization of the respective forms in the stomach on MR images as a function of the amount of water drunk, and also to determine the emptying rates of the two caffeine variants using saliva samples that were obtained in the study and quantified using LC-MS/MS. Gastric emptying of the ingested water was rapid and usually completed after approximately 20 min, regardless of the applied volume. In contrast to the consumed water, gastric emptying of natural caffeine and stable isotope labelled caffeine was delayed. The capsule usually floated on liquid and chyme, whereas the compression coated tablet was often embedded in chyme.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100365"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714209","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":"Transformative roles of digital twins from drug discovery to continuous manufacturing: pharmaceutical and biopharmaceutical perspectives","authors":"Ravi Maharjan ,&nbsp;Nam Ah Kim ,&nbsp;Ki Hyun Kim ,&nbsp;Seong Hoon Jeong","doi":"10.1016/j.ijpx.2025.100409","DOIUrl":"10.1016/j.ijpx.2025.100409","url":null,"abstract":"<div><div>Digital Twins (DTs) represent a groundbreaking development tool in the pharmaceutical and biopharmaceutical industries, providing virtual representations of physical entities, processes, or systems. This review investigates the transformative roles of DTs by examining their applications throughout the entire drug development lifecycle, from discovery to continuous manufacturing. By facilitating real-time monitoring and predictive analytics, DTs enhance operational efficiency, reduce costs, and improve product quality. Integration with advanced technologies, such as artificial intelligence and machine learning, further amplifies their capabilities, enabling sophisticated data analysis for preventive maintenance and manufacturing optimization. Despite these advantages, the implementation of DTs faces significant challenges, including data integration, model accuracy, and regulatory complexity. This review discusses these barriers while highlighting opportunities for innovation and automation through emerging technologies, including blockchain, nanotechnology, and dark factory. It also explores the potential of DTs to support personalized medicine through individualized treatments based on patient-specific data. Overall, this review highlights the current state, key challenges, and future perspectives of DT applications in pharmaceutical systems, emphasizing their potential to improve efficiency, quality, and patient outcomes.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100409"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216879","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":"Co-assembling de novo designed peptide with high-payload drug protein for noninvasive treatment of corneal neovascularization","authors":"Yuhua Tong ,&nbsp;Sijie Zhou ,&nbsp;Yongjie Guo ,&nbsp;Xiaoli Jin ,&nbsp;Meiting Yu ,&nbsp;Chunyun Feng ,&nbsp;Hao Chen ,&nbsp;Xingjie Zan ,&nbsp;Jinyang Li","doi":"10.1016/j.ijpx.2025.100410","DOIUrl":"10.1016/j.ijpx.2025.100410","url":null,"abstract":"<div><div>The specificity and low toxicity of protein drugs are significant for disease treatment but are strongly limited by their weak tissue penetrative capacity. Although formulating proteins with nanoparticle is an alternative strategy, the low encapsulation efficiency (EE) and loading capacity (LC) of protein drugs and their potential for protein inactivation remain significant challenges. Herein, the de novo designed peptide (Arg-His-Cys-Arg-His-Cys-Arg-His-Cys) (RHC)₃, zinc ions (Zn²⁺), and the anti-neovascular protein drug Bevacizumab (Beva) were co-assembled to form PZA@Beva (peptide and Zn²⁺ assemblies encaspsulated Beva) nanomedicine, aiming to overcome the challenges associated with corneal neovascularization (CNV) model. The optimized size of PZA@Beva is approximately 162.5 nm, with EE% and LC% of Beva 92.7 % and 55.8 %, respectively. The bioactivity of encapsulated Beva was preserved, protecting it from proteolytic degradation, and the release of Beva from PZA@Beva exhibited pH-dependent kinetics. In vitro, PZA@Beva demonstrated effective penetration across the ocular barrier via both the paracellular pathway (by opening corneal tight junctions) and the transcellular pathway (through rapid cellular endocytosis). Additionally, PZA@Beva exhibited no cytotoxicity in vitro or in vivo, coupled with prolonged ocular retention, collectively yielding promising results for the treatment of CNV. This study contributes to non-invasive protein delivery across ocular bio-barriers for the treatment of diseases in the anterior segment.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100410"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216957","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":"Ionic liquids self-assembled micelles for transdermal delivery: characterization, functions and applications","authors":"Ziqing Deng ,&nbsp;Shuwei Tang ,&nbsp;Mingjie Ou ,&nbsp;Zhuxian Wang","doi":"10.1016/j.ijpx.2025.100350","DOIUrl":"10.1016/j.ijpx.2025.100350","url":null,"abstract":"<div><div>Ionic liquid (ILs) self-assembled micelles (ILs-SAMs) are promising and effective drug delivery systems, which combine the merits of ILs and micelles. Herein, the properties, assembly, functions, and treatments of ILs-SAMs in transdermal drug delivery are summarized. This paper first reviews the fundamental concepts, classifications, assembly mechanisms, characterization techniques, and functional roles of ILs-SAMs. ILs-SAMs are micellar structures formed by the self-assembly of ILs through different intermolecular interactions, and are affected by multiple environmental factors. They possess unique physicochemical properties, endowing them with high stability and effective drug carriers, which could regulate their compositions and structures for flexible and controllable characteristics. Next, the review demonstrates that ILs-SAMs offer remarkable advantages in transdermal delivery, including solubilization enhancement, permeation enhancement, and targeted transdermal delivery. It alters the surface tension and viscosity of permeating substances, facilitates transdermal drug penetration, and utilizes nanoscale properties for precise, targeted delivery. Remarkably, ILs-SAMs were compared with other ILs self-assembled nanoparticles (ILs-SANPs) and polymer micelles, and the former possessed superior properties, including easier self-assembly and higher stability. Lastly, it focuses on their applications in treating skin cancer, arthritis, diabetes, fungal infections, and skin photoaging. Collectively, the novel ILs-SAMs are multifunctional transdermal drug delivery systems used for permeation enhancement, targeted drug delivery and different skin disorders.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100350"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524246","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":"A single oral administration of resveratrol cocrystals enables potent antisepsis therapy via interfering neutrophil extracellular traps formation","authors":"Juexian Wei ,&nbsp;Muhammad Inam ,&nbsp;Hengzong Mo ,&nbsp;Jiayu Huang ,&nbsp;Hongyu Zhao ,&nbsp;Aijia Zhong ,&nbsp;Xiaoyan Tang ,&nbsp;Ehua Deng ,&nbsp;Chuanshan Xu ,&nbsp;Xiaohui Chen ,&nbsp;Haifeng Mao ,&nbsp;Wenjie Chen ,&nbsp;Junrong Mo ,&nbsp;Yongcheng Zhu","doi":"10.1016/j.ijpx.2025.100386","DOIUrl":"10.1016/j.ijpx.2025.100386","url":null,"abstract":"<div><div>Sepsis is a life-threatening syndrome characterized by organ dysfunction resulting from host response disorders and is a common complication in patients suffering from clinical trauma, burns, and infections. Resveratrol, a natural polyphenol compound, possesses anti-inflammatory, antiviral, antibacterial, and antifungal properties, as well as cardiovascular and anti-tumor protective effects. However, its therapeutic applications have been limited due to low bioavailability, poor aqueous solubility, and rapid metabolism. To address these limitations, this study focused on the preparation of resveratrol (RES) cocrystal with nicotinamide (NCA) and RES polymorphs through recrystallization for oral application. The identity of the new crystalline forms was confirmed using powder X-ray diffraction (PXRD), Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and single-crystal X-ray diffraction (SCXRD). Physicochemical evaluations revealed that the RES polymorphs and RES-NCA cocrystal exhibited higher solubility and dissolution rates compared to pristine RES. In vitro experiments with LPS-stimulated HL-60 cells demonstrated that the RES-NCA cocrystal effectively inhibited neutrophil extracellular traps (NETs) formation by targeting peptidylarginine deiminase 4 (PADI4) and reducing inflammatory markers. Additionally, in vivo studies using a cecal ligation and puncture (CLP)-induced sepsis model in mice showed that oral administration of the RES-NCA cocrystal significantly reduced NETs formation, organ injury, and mortality. These findings suggest that orally administered RES-NCA cocrystal holds promise as a therapeutic agent for sepsis treatment, offering enhanced solubility and bioavailability, along with potent effects in inhibiting NETs formation and reducing sepsis-induced organ injury.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100386"},"PeriodicalIF":6.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004057","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}