Enhanced antitumor efficacy and decreased toxicity by self-associated docetaxel in phospholipid-based micelles

To overcome the poor aqueous solubility of docetaxel (DTX) and the side effects of the emulsifier in the marketed formulation, we have developed a DTX-loaded micelle using a nontoxic and biodegradable amphiphilic diblock copolymer, methoxy polyethylene glycol-distearoylphosphatidylethanolamine (mPEG(2000)-DSPE). The prepared micelles exhibited a core-shell structure, and DTX was successfully encapsulated in the core with an encapsulation efficiency of 97.31 ± 2.95% and a drug loading efficiency of 3.14 ± 0.13%. The micelles were spherical with a hydrodynamic diameter of approximately 20 nm, which could meet the requirement for in vivo administration, and were expected to enhance the drug's antitumor efficacy and to decrease its toxicity. To evaluate the DTX-loaded micelles, we chose a well marketed formulation, Taxotere(?), as the control. The prepared DTX micelle had a similar antiproliferative effect to Taxotere(?) in vitro but a significantly better antitumor efficacy than Taxotere(?) in vivo, which may be caused by passive targeting of the tumor by the micelles. In addition, the safety evaluation revealed that the DTX micelle was a qualified drug for use in vivo. Based on the experimental results, we propose that mPEG(2000)-DSPE micelle is a potent carrier for DTX.