ROS/pH dual-responsive quercetin-loaded guanosine borate supramolecular hydrogel enema in dextran sulfate sodium-induced colitis in mice

Ulcerative colitis (UC) is an inflammatory bowel disease that predominantly impacts the colon, typically starting in the rectum. A significant characteristic of UC is its propensity to affect the distal colon, which is particularly beneficial for targeted treatments such as enemas. This localized approach ensures that the medication is delivered directly to the affected areas, resulting in minimal systemic absorption. In this research, we have formulated a novel stimuli-responsive quercetin-loaded guanosine borate supramolecular hydrogel (named GBQ hydrogel), designed to prolong the residence time of the drug and protect the ulcerated intestinal tissues. The GBQ hydrogel has exhibited excellent injectability, self-healing capabilities, and biocompatibility, rendering it an ideal candidate for enema administration. In vitro studies have highlighted its ROS/pH dual-responsive release profile, which mimics the microenvironment of intestinal inflammation. Furthermore, we assessed the efficacy of the GBQ hydrogel on dextran sulfate sodium (DSS)-induced colitis, a common animal model for UC. Our findings indicate that the GBQ hydrogel significantly reduces disease activity, mitigates oxidative stress, restores the intestinal mucosal barrier, and prevents colonic cell apoptosis. Collectively, this study underscores the therapeutic potential of the GBQ hydrogel in managing inflammatory bowel conditions and paves the way for a novel hydrogel enema-based treatment strategy for UC.