Oral Delivery of Pterostilbene by L-Arginine-Mediated "Nano-Bomb" Carrier for the Treatment of Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of unknown aetiology affecting the colon and rectum. Pterostilbene (PS) has been reported as an effective antioxidant and anti-inflammatory agent in preclinical IBD models. However, the therapeutic outcomes of PS are limited by potential side effects associated with the systemic exposure and the modest bioavailability afforded by its oral administration. These issues can be improved with the use of intelligent responsive nanoparticles with the ability of lysosome escape, given their high drug delivery capacity and reducing the side effects. MATERIALS AND METHODS: Herein, the hyaluronic acid (HA)-modified L-arginine CO(2) nanoparticles (HA-L-Arg-CO(2)@NPs) loaded with PS (HA-PS@NPs) are constructed. Under lysosomal pH conditions, HA-PS@NPs liberate CO(2) and generate a pH-activated nano-bomb effect to augment the cytosolic delivery of PS. RESULTS: HA-L-Arg-CO(2)@NPs show great biocompatibility and the excellent ability to target the colon. Using lipopolysaccharide-induced inflammation in vitro, the prominent anti-inflammatory effect of HA-L-Arg-CO(2)@NPs and HA-PS@NPs is observed. Further, orally administered HA-L-Arg-CO(2)@NPs and HA-PS@NPs via the colon-targeted chitosan/alginate (CA) hydrogel downregulate pro-inflammatory cytokines and reduce intestinal permeability, yielding significant outcomes in alleviating the symptoms of UC. CONCLUSION: This pH-activated "nano-bomb" carrier with therapeutic effect can be exploited as efficient oral drug carriers for UC treatment.