姜黄素
化学
药理学
壳聚糖
药物输送
硫酸软骨素
体内
生物利用度
靶向给药
生物相容性
生物化学
医学
糖胺聚糖
生物
生物技术
有机化学
作者
Yinzhuo Xie,Wei Xu,Zheng Jin,Kai Zhao
标识
DOI:10.1016/j.mtbio.2023.100617
摘要
Curcumin (CUR) has a regulatory effect on the gut microbiota (GM), and its significant anti-inflammatory properties make it a research hotspot for inflammatory bowel disease (IBD) treatment. However, the low bioavailability and poor pharmacokinetic properties of CUR limit its practical application. Herein, CD44 and GM dual-targeted nanoparticles (NPs) loaded with CUR (CUR@Chs-PNC NPs) were derived from a quaternized chitosan and surface functionalization with chondroitin sulfate (Chs). The generated CUR@Chs-PNC NPs had an ideal average particle size (238.9 nm), a uniform size distribution, and a positive surface charge (+41.93 mV). Strikingly, the CUR@Chs-PNC NPs had a good sustained-release effect in a simulated gastrointestinal environment and exhibited the full drug release when in a simulated colon environment. Moreover, Chs functionalization endowed the NPs with a notable CD44-targeted drug delivery ability and thereby enhanced the CUR content in the plasma of SD rats. The biodistribution of the CUR@Chs-PNC NPs in vivo indicated that the NPs could prolong the intestinal residence time, thereby promoting the interaction between CUR and GM. Most importantly, in a DSS-induced colitis mouse model, the CUR@Chs-PNC NPs decreased the disease activity index, improved the oxidative stress and inflammation condition, promoted the production of short-chain fatty acids (SCFAs), regulated immune cells, and maintained intestinal microbiome homeostasis. This study demonstrates that CUR@Chs-PNC NPs, which exhibit excellent biocompatibility and biodegradability, on-demand drug release property, and CD44 and GM dual-targeted capacities, have the potential for further application in the treatment of colitis.
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