Preparation and biological activity studies of resveratrol loaded ionically cross-linked chitosan-TPP nanoparticles

Nanoparticles with size range of 10-500 nm can be efficiently delivered into cancer cells by the Enhanced Permeability and Retention (EPR) effect. Here, we prepared resveratrol (Res) loaded chitosan (CS) nanoparticles with the size of 172-217 nm by an ionic cross-linking method, with sodium tripolyphosphate (TPP) as the cross-linking agent, to improve the stability, solubility and tumors targeting of the natural anti-cancer drug Res. The prepared Res loaded CS-TPP nanoparticles presented long-term storage stability and UV light stability. The cumulative drug release from nanoparticles in mimetic tumor tissue condition (pH 6.5) was higher than that in physiological condition (pH 7.4). Further, Res-loaded CS-TPP nanoparticles maintained the antioxidant activity of Res even after UV light irradiation. Cell viability study shows that the as prepared drug loaded nanoparticles had similar antiproliferative activity on hepatocellular carcinoma cells SMMC 7721 and lower cytotoxicity on normal hepatocyte cells L02 compared with free Res. Fluorescence microscopy observation revealed that the nanoparticles were efficiently taken in by SMMC 7721 cells. This work indicates the potential use of drug loaded CS-TPP nanoparticles for the efficient delivery of bioactive Res for chemotherapy.