Abstract:The incidence of inflammatory bowel disease（IBD）has been increasing in recent years. Owing to the limitations of conventional drug therapies，the natural bioactive substances loaded by nanoparticles have emerged as a captivating avenue for potential treatment. Thin-film dispersion and high-pressure homogenization were employed to develop chitosan（CS）-modified astaxanthin（AST）-loaded nanoparticles（CS-ASTNPs）.The nanoparticles were evaluated in terms of particle size，Zeta potential，encapsulation efficiency（EE），and in vitro release assay.A mouse model of dextran sodium sulfate（DSS）-induced ulcerative colitis was established to evaluate the alleviating effect of CS-AST-NPs on colitis. The results demonstrated that CS-AST-NPs had an average particle size of 36 nm，Zeta potential of 30.77 mV，EE of 91.91%，and good storage stability.The CS-AST-NPs exhibited sustained release in the simulated gastrointestinal environment. Moreover，the CSAST-NPs alleviated the clinical symptoms of DSS-induced colitis in mice，which included maintaining body weight，reducing disease activity index，inhibiting colon shortening，alleviating histopathological damage，and improving the integrity of epithelial cells.More importantly，CS-AST-NPs substantially lowered the levels of proinflammatory cytokines and ameliorated DSS-induced oxidative damage in the inflamed colon tissue. Over all，the results suggested that CS-AST-NPs held great promise as a novel therapy for the treatment of IBD.