pH Sensitive Quercetin Nanoparticles Ameliorate DSS‐Induced Colitis in Mice by Colon‐Specific Delivery

Scope Ulcerative colitis (UC) is a classic inflammatory bowel disease (IBD) that represents a serious threat to human health. As a natural flavonoid with multiple biological activities, quercetin (QCT) suffers from low bioavailability through limitations in chemical stability. Here, the study investigates the regulatory effects of quercetin nanoparticles (QCT NPs) on dextran sulfate sodium (DSS) induced colitis mice. Methods and results Chitosan is modified to obtain N‐succinyl chitosan (NSC) with superior water solubility. Nanoparticles composed of sodium alginate (SA) and NSC can encapsulate QCT after cross‐linking, forming QCT NPs. In vitro drug release assays demonstrate the pH sensitivity of QCT NPs. Compared with free quercetin, QCT NPs have better therapeutic efficacy in modulating gut microbiota and its metabolites short chain fatty acid (SCFAs) to relieve DSS‐induced colitis in mice, thereby alleviating colon inflammatory infiltration, increasing goblet cells density and mucus protein, ameliorating TNF‐α, IL‐1β, IL‐6, IL‐10, and Myeloperoxidase (MPO) levels, and recovering intestinal barrier integrity. Conclusion pH sensitive QCT nanoparticles can reduce inflammatory reaction, improve gut microbiota, and repair intestinal barrier by targeting colon, thus improving DSS induced colitis in mice, providing reference for the treatment of colitis. Quercetin‐encapsulated nanoparticles (QCT‐NPs) are prepared by N‐succinyl chitosan (NSC) and sodium alginate (SA), and released at intestinal pH. QCT NPs alleviates dextran sulfate sodium (DSS)‐induced ulcerative colitis by suppressing pro‐inflammatory cytokines (TNF‐α, IL‐1β, and IL‐6) and Myeloperoxidase (MPO), facilitating levels of the anti‐inflammatory cytokine IL‐10 and tight junction proteins to restore intestinal barrier integrity, regulating intestinal flora and its metabolites.