Resveratrol liposomes in buccal formulations, an approach to overcome drawbacks limiting the application of the phytoactive molecule for chemoprevention and treatment of oral cancer

Abstract

Resveratrol is currently considered for chemoprevention and treatment of oral cancer, but unfavorable properties of this molecule hinder its clinical use. The present study deals with preparation of resveratrol liposomes by a method that preserves stability and provides payload high enough for chemoprevention and/or treatment of oral cancer. Different temperatures, resveratrol concentrations and molar fractions, as well as the presence or absence of vitamin C in the hydration media were assayed. Liposome hydrodynamic diameter, polydispersity and zeta potential were evaluated by dynamic light scattering. In vitro cytotoxicity, antioxidant activity, and permeability were evaluated using TR146 cells and PermeaPad® membranes. Liposomes were included in hydrogels and films, and their suitability for buccal application was evaluated by in vitro assays. A temperature of 37 °C was optimal to efficiently produce resveratrol liposomes. Vitamin C was found to influence liposome size, while resveratrol concentration significantly influenced entrapment efficiency. Cytotoxicity assay showed high biocompatibility while potent antioxidant activity, the inclusion of vitamin C reinforcing the latter effect. High permeation across membranes and efficient uptake by cells was proved for resveratrol liposomes. Liposomal hydrogels and films were obtained with payload high enough to produce mucosa concentrations above resveratrol IC50 values reported for cancer cells.