Preparation and Characterization of Tributyrin Sub-micron Emulsion as Carrier for Paclitaxel

Abstract

ABSTRACT − Paclitaxel is a well known anticancer agent and has been a pharmaceutical challenge because of itsextremely poor water-solubility and susceptibility to the p-glycoprotein (p-gp)-mediated efflux in multi-drug resistant(MDR) cancer cells. Tributyrin (TB), a triglyceride with relatively short fatty acid chains, was chosen as solubilizing vehiclefor paclitaxel based on the solubility study (26.6 mg/mL). Tributyrin (10%) o/w emulsion containing paclitaxel (5%), eggphosphatidylcholine (5%) and pegylated phospholipid (0.5%) was prepared by high pressure homogenization to obtain sub-micron-sized emulsion. The mean particle size of the resultant TB emulsion was 395.5 nm. Paclitaxel in TB emulsionshowed higher anticancer activity against human breast cancer cell line, MCF-7, than free form delivered in DMSO solution.On the other hand, its anticancer activity was significantly reduced in MCF-7/ADR, a MDR variant cancer cell line of MCF-7, and recovered by the presence of verapamil, suggesting of the susceptibility to the p-gp mediated efflux even thoughpaclitaxel was encapsulated into emulsion. The TB emulsion showed great potential as a promising vehicle for water-insol-uble anticancer agent, paclitaxel.Key words