Resveratrol loaded PLGA:D-α-tocopheryl polyethylene glycol 1000 succinate blend nanoparticles for brain cancer therapy

Abstract

trans-Resveratrol (RSV) is a natural molecule proved for cancer preventive and therapeutic activities without any potential side effects. In recent years, RSV is also proved for its cytotoxic potential against glioma. However, practical application of RSV in glioma chemotherapy is limited because of its low systemic circulation time and short biological half-life resulting from rapid metabolism and accelerated elimination from the blood pool. Therefore, the main objective of this study was to enhance systemic circulation time and short biological half-life of RSV using poly(d,l-lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate blend nanoparticles (RSV-PLGA-BNPs). RSV-PLGA-BNPs were successfully formulated and optimized by a single-emulsion solvent-evaporation technique. RSV-PLGA-BNPs were evaluated by various state of the art techniques for extensive nanoparticulate characterization. Cytotoxicity against C6 cells, cellular internalization and haemocompatibility were studied for proving anticancer potential and safety of RSV-PLGA-BNPs. Pharmacokinetic and tissue distribution studies were carried out in Charles Foster rats after intravenous (i.v) administration. RSV-PLGA-BNPs showed significantly higher cytotoxicity and excellent cell internalization in C6 glioma cells. Haemocompatibility studies suggested that RSV-PLGA-BNPs are safe for i.v administration. Pharmacokinetic studies showed prolonged systemic circulation of RSV-PLGA-BNPs up to 36 h with approximately 18.11 times higher plasma half-life than RSV solution. Tissue distribution studies showed higher brain accumulation of RSV-PLGA-BNPs than RSV. Therefore, RSV-PLGA-BNPs can be applied as a potential tool for enhancing systemic circulation and plasma half-life with superior anticancer efficacy against glioma. © 2016 The Royal Society of Chemistry.