H2S-releasing adhesive hydrogel as oral radioprotectant for gastrointestinal tract radioprotection

Abstract

Radiation damage can cause a series of gastrointestinal (GI) tract diseases. The development of safe and effective GI tract radioprotectants still remains a great challenge clinically. Here, we firstly report an oral radioprotectant Gel@GYY that integrates a porous gelatin-based (Gel) hydrogel and a pH-responsive hydrogen sulfide (H2S) donor GYY4137 (morpholin-4-ium 4 methoxyphenyl(morpholino) phosphinodithioate). Gel@GYY has a remarkable adhesion ability and long retention time, which not only enables responsive release of low-dose H2S in stomach and subsequently sustained release of H2S in the whole intestinal tract especially in the colon, but also ensures a close contact between H2S and GI tract. The released H2S can effectively scavenge free radicals induced by X-ray radiation, reduce lipid peroxidation level, repair DNA damage and recover vital superoxide dismutase and glutathione peroxidase activities. Meanwhile, the released H2S inhibits radiation-induced activation of nuclear factor κB (NF-κB), thus reducing inflammatory cytokines levels in GI tract. After treatment, Gel@GYY displays efficient excretion from mice body due to its biodegradability. This work provides a new insight for therapeutic application of intelligent H2S-releasing oral delivery system and potential alternative to clinical GI physical damage protectant.