Covalently crosslinked chitosan-astaxanthin nanoparticles: a stable, bioavailable oral delivery system with potentiated relief efficacy against chronic colitis.

Abstract

Background: Astaxanthin (AST) has potent antioxidant and anti-inflammatory properties; however, it is unstable and easily oxidized.

Results: In this study, chitosan (CS) was employed to stabilize AST through covalent crosslinking to synthesize chitosan-astaxanthin (CS-AST) complex, and then self-assembled into chitosan-astaxanthin nanoparticles (CS-ASTNPs). CS-ASTNPs showed a smooth, spherical morphology with a particle size of 102.6 ± 1.3 nm. The hydrodynamic particle size was 141.8 ± 1.7 nm with a zeta potential of 30.5 ± 1.4 mV. The encapsulation efficiency and loading capacity of AST within CS-ASTNPs were 83.6% and 46.1%, respectively. In a chronic colitis model induced by dextran sulfate sodium (DSS), CS-ASTNPs significantly improved the symptoms in mice body weight, colon length, and disease activity index (DAI) scores caused by DSS. The colon barrier was enhanced through increasing the level of the proteins ZO-1, occludin, and MUC2. Furthermore, the overproduction of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β), and the proteins NLRP3, ASC, Caspase-1, GSDMD, and cleaved Caspase-1 were reduced, while the anti-inflammatory cytokine interleukin 10 (IL-10) increased. The oxidative response in colon tissues was suppressed via regulating the Nrf2/HO-1 pathway. Additionally, CS-ASTNPs increased the Bacteroidetes/Firmicutes ratio and elevated the richness of beneficial bacteria norank_f__Muribaculaceae, Lactobacillus, and Akkermansiaceae. Notably, CS-ASTNPs showed significantly greater improvement than CS + AST (P < 0.05).

Conclusion: In sum, CS-ASTNPs has significant potential for development as a functional food or as a drug for treating colitis. © 2026 Society of Chemical Industry.