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生物活性壳聚糖-牛血清白蛋白美拉德反应衍生的载白杨素纳米颗粒:一种用于溃疡性结肠炎强化口服治疗的胃保护、生物黏附方法。

Bioactive chitosan-BSA Maillard-derived chrysin-loaded nanoparticles: A gastroprotective, biomucoadhesive approach for enhanced oral therapy in ulcerative colitis.

作者信息

Jori Chandrashekhar, Ahmad Anas, Kumar Ajay, Kumar Bhuvnesh, Ali Aneesh, Ali Nemat, Tabassum Heena, Khan Rehan

机构信息

Chemical Biology Unit, Institute of Nano Science and Technology, Sector 81, Knowledge city, Sahibzada Ajit Singh Nagar, Mohali, Punjab 140306, India.

Julia McFarlane Diabetes Research Centre (JMDRC), Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Hotchkiss Brain Institute, Cumming School of Medicine, Foothills Medical Centre, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

出版信息

Carbohydr Polym. 2025 Jul 1;359:123537. doi: 10.1016/j.carbpol.2025.123537. Epub 2025 Apr 5.

DOI:10.1016/j.carbpol.2025.123537
PMID:40306769
Abstract

The current limitations of oral nanomedicines such as aminosalicylates, immunosuppressants, corticosteroids, and antibiotics include the toxic byproducts from nanocarrier synthesis, poor targeting and retention within the inflamed colon, delayed release at inflammation sites, susceptibility to gastric degradation, reduced efficacy under hypoxic conditions, MUC2 homeostasis disruption, and insufficiently addressing the disease's root causes. This research presents an innovative approach of using non-toxic, biodegradable, and biocompatible Maillard reaction-based nanoparticles (MPs) for targeted oral drug delivery in IBD therapy. Through the development of mucoadhevise chitosan-bovine serum albumin Maillard nanoparticles shielded with biocompatible, non-toxic, non-immunogenic, gastroprotective pectin (P@CMPs) encapsulating with chrysin, a flavonoid with anti-inflammatory and hyperoxia properties whose bioavailability is negatively affected by gastric degradation. P@CMPs had a spherical, uniform 300 nm hydrodynamic diameter, confirmed by TEM and FESEM. Chrysin encapsulation efficiency and loading capacity were ∼96 % and 16 %, respectively, demonstrating effective nanoparticle formulation The P@CMPs is designed to withstand the gastrointestinal environment, ensuring targeted delivery and prolonged retention in inflamed colonic regions. In a dextran sodium sulfate-induced colitis mouse model, P@CMPs markedly mitigated inflammation, suppressed proinflammatory cytokine levels, and augmented the expression of MUC2, a crucial factor for maintaining the integrity of the gut barrier. By employing non-toxic, biocompatible and biodegradable materials, our P@CMPs approach offers a promising avenue for advancing IBD treatment, addressing various challenges and precise oral delivery within the gastrointestinal system.

摘要

目前口服纳米药物(如氨基水杨酸盐、免疫抑制剂、皮质类固醇和抗生素)的局限性包括纳米载体合成产生的有毒副产物、在炎症结肠内的靶向性和滞留性差、在炎症部位的释放延迟、易受胃降解影响、在缺氧条件下疗效降低、MUC2稳态破坏以及未能充分解决疾病的根本原因。本研究提出了一种创新方法,即使用基于无毒、可生物降解且生物相容的美拉德反应的纳米颗粒(MPs)用于炎症性肠病(IBD)治疗中的靶向口服给药。通过开发用生物相容、无毒、无免疫原性、具有胃保护作用的果胶(P@CMPs)包覆的粘膜粘附性壳聚糖 - 牛血清白蛋白美拉德纳米颗粒,该纳米颗粒包裹了白杨素,一种具有抗炎和抗高氧特性的黄酮类化合物,其生物利用度受到胃降解的负面影响。通过透射电子显微镜(TEM)和场发射扫描电子显微镜(FESEM)证实,P@CMPs具有球形、均匀的300nm流体动力学直径。白杨素的包封率和载药量分别约为96%和16%,表明纳米颗粒制剂有效。P@CMPs旨在耐受胃肠道环境,确保在炎症结肠区域的靶向递送和延长滞留时间。在葡聚糖硫酸钠诱导的结肠炎小鼠模型中,P@CMPs显著减轻炎症,抑制促炎细胞因子水平,并增强MUC2的表达,MUC2是维持肠道屏障完整性的关键因素。通过使用无毒、生物相容和可生物降解的材料,我们的P@CMPs方法为推进IBD治疗、应对各种挑战以及在胃肠道系统内实现精确口服递送提供了一条有前景的途径。

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