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

Int J Pharm. 2024 May 25:657:124143. doi: 10.1016/j.ijpharm.2024.124143. Epub 2024 Apr 23.

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.

Keywords: Bovine serum albumin; Diallyltrisulfide; Gas therapy; Gastric ulcers; Nanoparticle.

MeSH terms

  • Allyl Compounds* / chemistry
  • Allyl Compounds* / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Cytokines / metabolism
  • Ethanol* / chemistry
  • Gastric Mucosa* / drug effects
  • Gastric Mucosa* / metabolism
  • Glutathione / metabolism
  • Humans
  • Hydrogen Sulfide* / chemistry
  • Male
  • Mice
  • NF-kappa B / metabolism
  • Nanoparticles* / chemistry
  • Serum Albumin, Bovine* / chemistry
  • Stomach Ulcer* / chemically induced
  • Stomach Ulcer* / drug therapy
  • Sulfides* / administration & dosage
  • Sulfides* / chemistry
  • Sulfides* / pharmacology

Substances

  • Sulfides
  • Ethanol
  • Allyl Compounds
  • diallyl trisulfide
  • Hydrogen Sulfide
  • Serum Albumin, Bovine
  • Glutathione
  • Cytokines
  • NF-kappa B