Colon Enzyme‐Activated Prebiotic Nanomedicine for Targeted Therapy of Inflammatory Bowel Disease

Abstract Inflammatory bowel disease is commonly treated with conventional therapies that suffer from poor drug bioavailability and significant side effects. This work develops a nanoparticle system using inulin, a naturally occurring polysaccharide, to address these challenges. This colon‐targeted oral drug delivery system enables precise and efficient treatment of IBD by leveraging the colon‐specific degradation of inulin by the enzyme inulinase. The nanoparticles demonstrate high stability in the upper gastrointestinal tract and ensure the release of the drug payload in the colon, triggered by inulinase activity. In mouse models, oral administration of these nanoparticles, both with and without drug loading, significantly reduce body weight loss, preserve colon length, and exhibit synergistic anti‐inflammatory effects. Notably, even the nanoparticles without drug loading are effective in reducing inflammation and oxidative stress, likely due to the antioxidant properties of inulin. Additionally, the use of inulin promotes a beneficial shift in gut microbiota by decreasing pathogenic bacteria and increasing beneficial bacterial populations, further enhancing its therapeutic potential. These findings suggest that these prebiotic nanoparticles offer a targeted and effective strategy for IBD treatment by both anti‐inflammatory benefits and microbiota modulation. This study highlights the potential of prebiotic‐based nanomedicine for the treatment of IBD and possibly other colon‐related diseases.