Epidemiological and clinical studies compellingly documented the ability of Mediterranean diet rich in extra-virgin olive oil (EVOO) to reduce breast and colon cancers incidence, cardiovascular diseases, and aging cognitive functions decline. (-)-Oleocanthal (OC) and other EVOO phenolics gain progressive research attention due to their documented biological effects against cancer, inflammations, and Alzheimer’s disease. There is no simple, reliable, and cost-effective isolation protocol for EVOO phenolics, which hinder their therapeutic applications. This study develops novel methods to isolate OC and other EVOO phenolics. This includes the use of ultra-freezing to eliminate most EVOO fats and the successful water capacity to efficiently extract OC and EVOO phenolics as self-emulsified nano-emulsion. Subsequent resin entrapment and size exclusion chromatography afforded individual EVOO phenolics in high purity. OC in vitro and in vivo oral anti-breast cancer (BC) activities validated its lead candidacy. Effective isolation of EVOO phenolics provided in this study will facilitate future preclinical and clinical investigations and stimulate the therapeutic development of these important bioactive natural products.

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Among two groups of components of Vitamine E, tocopherols and tocotrienols (T3), T3 shown to have anticancer property. It has been also reported that T3 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 T3 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 T3 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 IC50 of the T3-Simvastatin combination nanoemuslion was found 10.3 ȝM for MCF-7 and 4.8 ȝM for MDA-MB-231 cells which is significantly lower than T3 nanoemulsion which showed IC50 of 14 ȝM and 7 ȝM and Simvastatin alone which showed IC50 of 19 ȝM and 8 ȝM 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.

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