Dual targeting procyanidin nanoparticles with glutathione response for colitis treatment

The purpose of this study is to design a cell membrane and mitochondrial targeting nanoparticle with glutathione stimulus response to deliver procyanidin for effective treatment of inflammatory bowel disease (IBD). The dual targeting procyanidin nanoparticles were prepared with amphiphilic stearic acid modified hyaluronic acid using cystamine dihydrochloride as a linker for encapsulation of (5-carboxypentyl) (triphenyl) phosphonium bromide conjugated procyanidins. As expected, the procyanidin nanoparticles showed good mitochondrial targeting ability, with a Pearson's correlation coefficient of 0.91 at 4 h. In vivo imaging of IBD mice model demonstrated a remarkable colon accumulation of the targeting procyanidin nanoparticles. Significant glutathione stimulus release of procyanidin was found in the presence of 10 mM of glutathione at pH 7.4. In vivo experiments showed that the colon length of targeting procyanidin nanoparticle-treated IBD mice increased by 20.84% compared with the IBD mice. The weight loss, disease activity index score, oxidative stress level and the release of proinflammatory cytokines were significantly ameliorated. The composition and relative abundance of gut microbiota, and the number of short chain fatty acids were improved upon the uptake of targeting procyanidin nanoparticles. This study provided a dual targeting and glutathione response strategy to improve the bioavailability of procyanidin in IBD treatment.