Combination Therapy using Co-encapsulated Resveratrol and Paclitaxel in Liposomes for Drug Resistance Reversal in Breast Cancer Cells in vivo.

Multidrug resistance (MDR) is a major impediment to cancer treatment. A promising strategy for treating MDR is the joint delivery of combined anticancer agents to tumor cells in a single nanocarrier. Here, for the first time, Resveratrol (Res) was co-encapsulated with paclitaxel (PTX) in a PEGylated liposome to construct a carrier-delivered form of combination therapy for drug-resistant tumors. The composite liposome had an average diameter of 50 nm with encapsulated efficiencies of above 50%. The studies demonstrated that the composite liposome could generate potent cytotoxicity against the drug-resistant MCF-7/Adr tumor cells in vitro and enhance the bioavailability and the tumor-retention of the drugs in vivo. Moreover, systemic therapy with the composite liposome effectively inhibited drug-resistant tumor in mice (p < 0.01), without any notable increase in the toxicity. These results suggested that the co-delivery of Res and a cytotoxic agent in a nanocarrier may potentially improve the treatment of drug-resistant tumors.