Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Pharmaceutics, School of Pharmacy, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Carbohydr Polym. 2023 Aug 1;313:120884. doi: 10.1016/j.carbpol.2023.120884. Epub 2023 Apr 11.
Based on the biocompatibility and macrophage targeting of natural polysaccharides, combined with the physiological and pathological characteristics of the gastrointestinal tract and colonic mucosa of ulcerative colitis (UC), we prepare dexamethasone (Dex)-loaded oral colon-targeted nano-in-micro drug delivery systems coated with multilayers of chitosan (CS), hyaluronic acid (HA), and finally Eudragit S100 (ECHCD MPs) using a layer-by-layer coating technique for UC treatment through regulating the M1/M2 polarization of intestinal macrophages. HA/CS/Dex nanoparticles (HCD NPs) are ingested by macrophages via CD44 receptor-mediated endocytosis to regulate M1-to-M2 macrophage polarization and exert anti-inflammatory effects. Moreover, ECHCD MPs show better colon-targeting properties than Dex-loaded chitosan nanoparticles (CD NPs) and HCD NPs which is demonstrated by stronger mucoadhesion to inflamed colon tissues. After oral administration, ECHCD MPs exert significant anti-UC effects. Therefore, ECHCD MPs are proven to be as promising oral colon-targeting drug delivery systems for Dex and have potential application in UC treatment.
基于天然多糖的生物相容性和巨噬细胞靶向性，结合溃疡性结肠炎（UC）胃肠道和结肠黏膜的生理和病理特征，我们制备了载有地塞米松（Dex）的口服结肠靶向纳米-微药物传递系统，该系统采用层层涂层技术，用壳聚糖（CS）、透明质酸（HA）和最后 Eudragit S100（ECHCD MPs）进行涂层，通过调节肠道巨噬细胞的 M1/M2 极化来治疗 UC。HA/CS/Dex 纳米粒（HCD NPs）通过 CD44 受体介导的内吞作用被巨噬细胞摄取，以调节 M1 向 M2 巨噬细胞极化并发挥抗炎作用。此外，ECHCD MPs 表现出比载有地塞米松的壳聚糖纳米粒（CD NPs）和 HCD NPs 更好的结肠靶向特性，这表现在对发炎结肠组织具有更强的粘膜粘附性。口服给药后，ECHCD MPs 对 UC 具有显著的治疗作用。因此，ECHCD MPs 被证明是有前途的 Dex 口服结肠靶向药物传递系统，并有可能应用于 UC 的治疗。
