Development of docetaxel-loaded vitamin E TPGS micelles: formulation optimization, effects on brain cancer cells and biodistribution in rats

Abstract

Aim: This work aimed to develop docetaxel-loaded D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) micelles for brain cancer chemotherapy by taking advantage of polyethylene glycol for its long half-life in circulation and vitamin E for its high cellular uptake. Material & methods: TPGS micelles containing docetaxel or coumarin-6 were prepared by the solvent casting method and the direct dissolution method at high, moderate and low drug-loading levels. Results & discussion: The particle size of the docetaxel-loaded TPGS micelles ranged between 12 and 14 nm. Docetaxel formulated in the TPGS micelles of high, moderate and low drug-loading levels achieved lower IC50 values compared with Taxotere® after 24-h incubation with C6 glioma brain cancer cells. The TPGS has much lower critical micelle concentration than most phospholipids in micellar formulation, which can be an efficient drug carrier across the blood brain–barrier with high drug encapsulation efficiency, cell uptake, cytotoxicity and desired biodistribution of the formulated drug. Original submitted: 21 March 2011; Revised submitted: 14th June 2011