Stability and in vitro antiproliferative activity of bioactive “Vitamin E” fortified parenteral lipid emulsions

The objectives of this work were to engineer physically stable “Vitamin E” rich intravenous lipid emulsions and to evaluate their in vitro antiproliferative activity against MCF-7 (human mammary adenocarcinoma) and SW-620 (human colon adenocarcinoma) cell lines. Emulsions loaded with 70% vitamin E by total weight of the oil phase were stabilized with secondary emulsifiers and tested for their hemolytic effect and their plasma and electrolyte stability. Emulsions stabilized with sodium oleate and sodium deoxycholate were sensitive to electrolytes and exhibited significant hemolytic effect. On the other hand, addition of 2.5% poloxamer was found to stabilize the emulsions against electrolytes and physical stress, which was attributed to the steric effect of their polyoxyethylene (POE) head group. When tested for their antiproliferative effects, poloxamer-stabilized tocotrienol lipid emulsions were found to exhibit significantly higher anticancer activity than lipid emulsions enriched with tocopherol alone. The half maximal inhibitory concentrations (IC50) of tocotrienols lipid emulsions against MCF-7 and SW-620 were 14 and 12 μM, respectively, whereas the IC50s of tocopherol lipid emulsions were approximately 69 and 78 μM against MCF-7 and SW-620 cells, respectively.

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► Secondary co-emulsifier is required for emulsions fortified with high vitamin E loads.
► Emulsion stabilized with Na oleate and Na deoxycholate are sensitive to electrolyte.
► Na oleate and deoxycholate in emulsions induce hemolysis and coalescence in plasma.
► Poloxamer® 188 is an optimal co-emulsifier when preparing vitamin E lipid emulsions.
► Tocotrienols are more cytotoxic than tocopherol against human breast and colon cancer.