Simultaneous Delivery of Tocotrienols and Simvastatin by Lipid Nanoemulsion: A Promising Approach for Enhanced Antitumor Activity Against Human Mammary Adenocarcinoma Cells

Summary form only given. Among two groups of components of Vitamine E, tocopherols and tocotrienols (T
₃
), T
₃
shown to have anticancer property. It has been also reported that T
₃
potentiate the anticancer activity of some other drugs including statins when delivered simultaneously. Therefore, our study was designed to formulate a stable nanoemulsion as platform for simultaneous delivery of T
₃
and Simvastatin and evaluate the antiproliferative activity of the nanoemulsion against MCF-7 and MDA-MB-231 human mammary tumor cells. Nanoemuslion were prepared by high pressure homogenization where 9% w/w Simvastatin was loaded in T
₃
and medium chain triglyceride 70/30 blend. Mixture of primary and secondary emulsifier with DI water was used as aqueous phase. The size of the droplets was about 200nm and zeta potential was -45mV. Morphology were investigated with scanning transmission electron microscopy and found spherical or spheroidal in shape. Stability of the formulation was observed for 6 months and found stable with no loss in simvastatin loading. It has been found that, approximately 20% of Simvastatin was released in 24hrs at 37°C under sink condition. The IC
₅₀
of the T
₃
-Simvastatin combination nanoemuslion was found 10.3 μM for MCF-7 and 4.8 μM for MDA-MB-231 cells which is significantly lower than T
₃
nanoemulsion which showed IC
₅₀
of 14 μM and 7 μM and Simvastatin alone which showed IC
₅₀
of 19 μM and 8 μM for MCF-7 and MDA-MB-231 cells consecutively. The present study demonstrate that, parenteral lipid nanoemulsion is a promising platform for simultaneous delivery of anticancer drugs.