Colon-Targeting Angelica sinensis Polysaccharide Nanoparticles with Dual Responsiveness for Alleviation of Ulcerative Colitis

作者：Yu Xu, Beiwei Zhu, Rong Sun, Xiang Li, Di Wu, Jiangning Hu · 发表于：ACS Applied Materials & Interfaces · 年份：2023 · DOI：10.1021/acsami.3c02128 · 被引用次数：64 · 研究领域：Inflammatory Bowel Disease、Tryptophan and brain disorders、Gut microbiota and health

Intestinal immune dysfunction and gut microbiota dysbiosis are critically causative factors in the pathogenesis of ulcerative colitis (UC); however, the current first-line drugs for UC treatment in clinics often remain great challenges due to their nontargeting therapeutic efficacy and severe side effects. In the current study, colon-targeting nanoparticles based on Angelica sinensis polysaccharide with pH- and redox-responsiveness were fabricated to specifically release the naturally active compound ginsenoside Rh 2 in the colonic inflammatory site, which greatly alleviated the UC symptoms and improved the gut microbial homeostasis. These dual responsive Rh 2 -loaded nanoparticles (Rh 2 /LA-UASP NPs) with a particle size of 117.00 ± 4.80 nm were prepared using the polymer LA-UASP obtained by grafting A. sinensis polysaccharide with urocanic acid and α-lipoic acid (α-LA). As expected, these Rh 2 /LA-UASP NPs achieved dual pH- and redox-responsive drug release at pH 5.5 and 10 mM GSH. The stability, biocompatibility, and in vivo safety experiments exhibited these prepared nanoparticles had excellent colon-targeting ability and significant accumulation of Rh 2 in the inflammatory colon. Meanwhile, these Rh 2 /LA-UASP NPs could escape from lysosomes and be efficiently internalized into intestinal mucosal cells, thereby effectively inhibiting the release of proinflammatory cytokines. The animal experiments indicated that Rh 2 /LA-UASP NPs significantly improved the integrity of i...