Despite the known anticancer potential of resveratrol, its clinical applications are often hindered by physicochemical limitations such as poor solubility and stability. The encapsulation of resveratrol in formulations such as polymeric nanoparticles and liposomes has shown limited success. This study aimed to develop and optimize a novel drug carrier by co-encapsulating pristine resveratrol alongside cyclodextrin-resveratrol inclusion complexes in the lipophilic and hydrophilic compartments of liposomes, respectively by using a novel dual carrier approach. The particle size, polydispersity index and zeta potential of the final formulation were 131 +/- 1.30 nm, 0.089 +/- 0.005 and -2.64 +/- 0.51 mV, respectively. Compared to free resveratrol and conventional liposomal formulations with drug release profile of 40-60%, our novel nanoformulations showed complete (100%) drug release in 24 h. The formulation was stable for 14 days at 4 degrees C. We also studied the in vitro cytotoxicity of resveratrol encapsulated liposomes in HT-29 colon cancer cell lines. The cytotoxicity profile of our liposomes was observed to be dose dependent and enhanced in comparison to free resveratrol (in DMSO). Our study demonstrates that co-encapsulation of pristine resveratrol along with its cyclodextrin complex in liposomal formulations is a plausible option for the enhanced delivery of the hydrophobic chemotherapeutic agent. (C) 2015 Elsevier Inc. All rights reserved.