药理学
溃疡性结肠炎
炎症性肠病
生物利用度
药物输送
促炎细胞因子
毒品携带者
医学
结肠炎
姜黄素
口服
药品
壳聚糖
炎症
化学
免疫学
生物化学
内科学
疾病
有机化学
作者
Wei Wei,Yujie Zhang,Runqing Li,Yameng Cao,Xiangji Yan,Yana Ma,Yuanyuan Zhang,Mei Yang,Mingzhen Zhang
摘要
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of unknown aetiology affecting the colon and rectum. Pterostilbene (PS) has been reported as an effective antioxidant and anti-inflammatory agent in preclinical IBD models. However, the therapeutic outcomes of PS are limited by potential side effects associated with the systemic exposure and the modest bioavailability afforded by its oral administration. These issues can be improved with the use of intelligent responsive nanoparticles with the ability of lysosome escape, given their high drug delivery capacity and reducing the side effects.Herein, the hyaluronic acid (HA)-modified L-arginine CO2 nanoparticles (HA-L-Arg-CO2@NPs) loaded with PS (HA-PS@NPs) are constructed. Under lysosomal pH conditions, HA-PS@NPs liberate CO2 and generate a pH-activated nano-bomb effect to augment the cytosolic delivery of PS.HA-L-Arg-CO2@NPs show great biocompatibility and the excellent ability to target the colon. Using lipopolysaccharide-induced inflammation in vitro, the prominent anti-inflammatory effect of HA-L-Arg-CO2@NPs and HA-PS@NPs is observed. Further, orally administered HA-L-Arg-CO2@NPs and HA-PS@NPs via the colon-targeted chitosan/alginate (CA) hydrogel downregulate pro-inflammatory cytokines and reduce intestinal permeability, yielding significant outcomes in alleviating the symptoms of UC.This pH-activated "nano-bomb" carrier with therapeutic effect can be exploited as efficient oral drug carriers for UC treatment.
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