Concurrent delivery of tocotrienols and simvastatin by lipid nanoemulsions potentiates their antitumor activity against human mammary adenocarcenoma

Tocotrienol rich fraction (TRF) of vitamin E was previously shown to have anticancer activity against murine tumor cells in vitro. TRF was also shown to potentiate the anticancer activity of statins. The objectives of this study were therefore (a) to prepare and characterize stable parenteral lipid nanoemulsions as a novel platform for the concurrent delivery of TRF and simvastatin for subsequent use in combination chemotherapy, and (b) to evaluate the antiproliferative activity of the nanoemulsions against MCF-7 and MDA-MB-231 human mammary tumor cells. Nanoemulsions were prepared by the high-pressure homogenization technique using a viscous 70/30 blend of TRF and medium chain triglycerides as the oil phase in which simvastatin was dissolved at 9% w/w loading. Nanoemulsion droplets were about 200 nm in size and had surface potential of -45 mV. In a dissolution study, approximately 20% of simvastatin was released in sink conditions after 24 h. The stability of the nanoemulsions was monitored over 6 months of storage. No oxidation or degradation products were detected and no loss in simvastatin loading was observed during this period. The antiproliferative activity of the nanoemulsions was also retained after storage. The IC50 of the TRF nanoemulsions against MCF-7 and MDA-MB-231 was 14 and 7 mu M, respectively, which decreased to 10 mu M and 4.8 mu M when simvastatin was added to the nanoemulsions. Nanoemulsions prepared with tocopherol had no anticancer activity and were used as negative control. This study demonstrated that parenteral lipid nanoemulsions are viable delivery platform for potential use in cancer chemotherapy. (C) 2012 Elsevier B.V. All rights reserved.