Oral Prebiotic Polysaccharide Hydrogels Sustaining Colon Antibody Release Alleviate Inflammatory Bowel Disease

ABSTRACT Inflammatory bowel disease (IBD) is a chronic systemic immune disorder with unclear pathogenesis that involves complex interplay between inflammation, gut microbiota, and immune dysregulation. The advance of antibodies targeting tumor necrosis factor‐alpha and interleukin‐12/23, e.g., infliximab (IFX) and ustekinumab (UTK), has greatly improved the clinical treatments. The current intravenous dosing scheme, however, yields partial responses with potentially severe systemic side effects. Here, we report that oral prebiotic polysaccharide hydrogels based on inulin and alginate‐dopamine conjugate (predaGel) mediating efficient and sustained colon antibody delivery and reactive oxygen species (ROS) scavenging effectively alleviate IBD. predaGel with pH and enzyme dual responsiveness is stable in the stomach, adhesive to the intestine, and slowly degrading in the colon, resulting in site‐specific and controlled release of IFX. The mucosal retention, ROS scavenging, and gut microbiota remodeling properties endowed by dopamine and inulin in predaGel not only prevent diarrhea and suppress oxidative stress but also prolong drug function and restore immune homeostasis. Intriguingly, oral administration of IFX and/or UTK‐encapsulated predaGel cures IBD and restores colon function, offering an effective oral alternative to IFX injection. This oral prebiotic hydrogel strategy, with simplicity and multi‐functions, presents a potentially safer and better biologic therapy for IBD.