Oral colon targeted curcumin-based nanocomposite inulin hydrogel for alleviating intestinal inflammation and dysbiosis

Abstract Scavenging excess reactive oxygen species (ROS) and positively improving intestinal dysbiosis is a promising therapeutic strategy for alleviating inflammatory bowel disease (IBD). However, conventional clinical drugs and probiotic-based adjuvant therapies often fail to achieve satisfactory results due to systemic side effects of drugs, low bioactivity of probiotics, short intestinal retention time, and poor targeting ability. To address these challenges, we developed an antioxidant-functionalized curcumin loaded nanocomposite inulin hydrogel for targeted IBD therapy. In this system, curcumin was encapsulated within chitosan-coated Poly (lactic-co-glycolic acid) PLGA nanoparticles, which not only exhibited excellent ROS-scavenging capacity but also demonstrated the enhanced cellular uptake behavior. In a dextran sulfate sodium induced ulcerative colitis mouse model, the nanocomposite hydrogel significantly prolonged the intestinal retention time of curcumin, thereby suppressing the expression of pro-inflammatory factors, alleviating intestinal inflammation, and promoting the recovery of intestinal barrier and microbial diversity. This study has developed a synergistic therapeutic strategy via combining anti-inflammatory effects with gut microbiota regulation, offering a novel therapeutic approach for the clinical management of colitis. Graphical Abstract