Injectable Bioadhesive Hydrogels Scavenging ROS and Restoring Mucosal Barrier for Enhanced Ulcerative Colitis Therapy

Despitethe progress in the therapy of ulcerative colitis (UC),long-lasting UC remission can hardly be achieved in the majority ofUC patients. The key pathological characteristics of UC include animpaired mucosal barrier and local inflammatory infiltration. Thus,a two-pronged approach aiming at repairing damaged mucosal barrierand scavenging inflammatory mediators simultaneously might hold greatpotential for long-term remission of UC. A rectal formulation candirectly offer preferential and effective drug delivery to inflamedcolon. However, regular intestinal peristalsis and frequent diarrheain UC might cause transient drug retention. Therefore, a bioadhesivehydrogel with strong interaction with intestinal mucosa might be preferablefor rectal administration to prolong drug retention. Here, we designeda bioadhesive hydrogel formed by the cross-linking of sulfhydryl chondroitinsulfate and polydopamine (CS-PDA). The presence of PDA would ensurethe mucosa-adhesive behavior, and the addition of CS in the hydrogelnetwork was expected to achieve the restoration of the intestinalepithelial barrier. To scavenge the key player (excessive reactiveoxygen species, ROS) in inflamed colon, sodium ferulic (SF), a potentROS inhibitor, was incorporated into the CS-PDA hydrogel. After rectaladministration, the SF-loaded CS-PDA hydrogel could adhere to thecolonic mucosa to allow prolonged drug retention. Subsequently, sustainedSF release could be achieved to persistently scavenge ROS in inflammatoryareas. Meanwhile, the presence of CS would promote the restorationof the mucosal barrier. Ultimately, scavenging ROS and restoring themucosal barrier could be simultaneously achieved via this SF-loadedbioadhesive hydrogel scaffold. Our two-pronged approach might providenew insight for effective UC treatment.