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

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) phos-phinodithioate). Gel@GYY has a remarkable adhesion ability and long retention time, which not only en-ables 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 peroxida-tion level, repair DNA damage and recover vital superoxide dismutase and glutathione peroxidase activi-ties. Meanwhile, the released H2S inhibits radiation-induced activation of nuclear factor kappa B (NF-kappa B), 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.(c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.