Microbial enzyme-responsive inulin nanoparticles for colon-targeted oral delivery of 5-ASA toward improved therapy of inflammatory bowel disease

Colon-targeted delivery of 5-aminosalicylic acid (5-ASA) offers an effective strategy for treating inflammatory bowel disease (IBD) while minimizing systemic side effects. However, conventional oral 5-ASA formulations suffer from premature drug release and poor colon specificity. To overcome these limitations, we developed a biodegradable, prebiotic, and immunomodulatory inulin nanoparticle (INP) platform enabling microbial enzyme-responsive and site-specific release of 5-ASA in the colon. Methods: . Biodistribution of DiR-labeled INPs was analyzed to demonstrate colon-targeting efficacy. Therapeutic efficacy, inflammatory cytokine expression, Treg responses in the colon and gut-associated lymphoid tissues, and microbiota-related effects, including short-chain fatty acid (SCFA) production, were evaluated in a colitis mouse model. Results: < 0.001). Treatment increased the number of FOXP3+ cells in the colonic tissue and suppressed the expression of IL-17A, TNF-α, and IL-1β. The gut microbial profile was restored toward that of the normal group and fecal SCFA levels were increased. Conclusions: This study demonstrates that the INP platform enables microbial enzyme-responsive, colon-targeted delivery of 5-ASA while complementarily harnessing the intrinsic prebiotic and immunomodulatory properties of inulin. This dual-function nanoplatform provides a promising strategy for efficient oral treatment of IBD.