Lesion-targeted probiotic delivery via ROS-activated gelation and mucoadhesion for transanal treatment of colitis
Ulcerative colitis (UC) is a chronic inflammatory disorder of the colorectal mucosa, where conventional enema therapies suffer from poor retention and limited inflammation modulation. Here, we report a highly fluid probiotic-containing enema solution (s-BSA-Fe+EcN) integrating bovine serum albumin (BSA), Fe2+, and probiotic Escherichia coli Nissle 1917 (EcN). The solution's high fluidity enables comprehensive coverage of irregular colorectal mucosa. Upon encountering reactive oxygen species (ROS)-rich inflamed lesions, Fe2+ mediates H2O2 scavenging and hydroxyl radical generation, triggering BSA crosslinking and in situ gelation into a conformal hydrogel (h-BSA-Fe+EcN). This targeted adhesion mitigates oxidative damage to host tissues and preserves probiotic viability. In a porcine model, endoscopic imaging confirmed inflammation-targeted gelation in vivo. In a dextran sulfate sodium-induced mouse colitis model, h-BSA-Fe+EcN demonstrated excellent therapeutic efficacy, reducing disease activity index and restoring colonic architecture. This strategy addresses the dual challenges of fluid perfusion and rapid ROS-responsive gelation, offering an advanced transanal treatment for UC.