Construction of Gastrodin Nanocarriers and Their Improving Effect on Gastric Ulcers.

In the pathogenesis of gastric ulcer, mitochondrial dysfunction can exacerbate oxidative stress levels. Gastrodin (Gas), a key active component in food-drug homologous platycodon grandiflorum extract, exhibits significant anti-inflammatory and antioxidant properties. However, the complex gastrointestinal environment can pose limitations on the oral administration of free Gas, as is the case with many drugs. This study aimed to develop a mitochondrially functionalized (5-carboxypentyl) (triphenyl) phosphonium bromide (TPP) Gas nanoparticle system to effectively prevent ethanol-induced gastric ulcers in mice. Gas nanoparticles (Gas-NPs) were successfully synthesized through enzymatic reaction, followed by the synthesis of TPP mitochondrial-targeted functionalized Gas nanoparticles system (GT-NPs) through amide reaction. In vitro experiments demonstrated the efficient uptake of GT-NPs by human gastric epithelial cells (GES-1) with precise mitochondrial targeting and excellent antioxidant capabilities. Furthermore, GT-NPs exhibited gradual disintegration and release in simulated gastric fluid (SGF), effectively reducing oxidative stress, cell apoptosis, inflammatory infiltration, and the expression levels of PCNA and BAX proteins in gastric tissues of mice with ethanol-induced gastric ulcers. Collectively, our findings suggest that GT-NPs hold promise as targeted oral controlled release agents for the treatment of gastric ulcers.