Inulin Hydrogel Loaded with Self-Assembled Nanoparticles of Curcumin and Glycyrrhizic Acid for Inflammatory Bowel Disease Treatment via Anti-Inflammation, Antioxidation, and Microbiota Modulation

Inflammatory bowel disease (IBD) management remains challenging due to the inadequate efficacy and systemic toxicity of conventional therapies. Herein, we developed an inulin hydrogel loaded with self-assembled nanoparticles of curcumin and glycyrrhizic acid (CURG@IN) for IBD treatment. CURG@IN exhibited remarkable gel characteristics and enzyme-responsive drug release behavior. In vitro, CURG@IN demonstrated potent antioxidant capabilities, effectively protecting cells from oxidative injury, facilitating wound healing of epithelial cells, and regulating macrophage polarization. Additionally, it exerted inhibitory effects on the NF-κB pathway, thereby reducing the production of inflammatory cytokines. In DSS-induced colitis mice, oral CURG@IN significantly ameliorated disease activity index and restored colonic histological architecture. Gut barrier integrity was reinforced through upregulation of tight junction proteins, while microbiota analysis revealed significant restoration of microbial homeostasis. Notably, no significant toxicity was observed during treatment. Collectively, this oral therapeutic strategy provides a multimechanistic approach combining anti-inflammatory, antioxidative, and microbiota-modulating effects for safe IBD therapy, with the potential for clinical application.