Construction of diallyltrisulfide nanoparticles for alleviation of ethanol-induced acute gastric injury

Abstract

Gastric ulcer, a significant health issue characterized by the degradation of the gastric mucosa, often arises from excessive gastric acid secretion and poses a challenge in current medical treatments due to the limited efficacy and side effects of first-line drugs. Addressing this, our study develops a novel therapeutic strategy leveraging gas therapy, specifically targeting the release of hydrogen sulfide (H2S) in the treatment of gastric ulcers. We successfully developed a composite nanoparticle, named BSA·SH-DATS, through a two-step process. Initially, bovine serum albumin (BSA) was sulfhydrated to generate BSA·SH nanoparticles via a mercaptosylation method. Subsequently, these nanoparticles were further functionalized by incorporating diallyltrisulfide (DATS) through a precise Michael addition reaction. This sequential modification resulted in the creation of BSA·SH-DATS nanoparticles. Our comprehensive in vitro and in vivo investigations demonstrate that these nanoparticles possess an exceptional ability for site-specific action on gastric mucosal cells under the controlled release of H2S in response to endogenous glutathione (GSH), markedly diminishing the production of pro-inflammatory cytokines, thereby alleviating inflammation and apoptosis. Moreover, the BSA·SH-DATS nanoparticles effectively regulate critical inflammatory proteins, including NF-κB and Caspase-3. Our study underscores their potential as a transformative approach for gastric ulcer treatment.