Drug-interactive mPEG--PLA-Phe(Boc) micelles enhance the tolerance and anti-tumor efficacy of docetaxel.

Docetaxel (DTX) is one of the most promising chemotherapeutic agents for a variety of solid tumors. However, the clinical efficacy of the marketed formulation, Taxotere, is limited due to its poor aqueous solubility, side effects caused by the emulsifier, and low selective DTX distribution . Here a facile, well-defined, and easy-to-scale up DTX-loaded -(tert-butoxycarbonyl)--phenylalanine end-capped methoxy-poly(ethylene glycol)--poly(-lactide) (mPEG--PLA-Phe(Boc)) micelles (DTX-PMs) were prepared in an effort to develop a less toxic and more efficacious docetaxel formulation. The physicochemical properties, pharmacokinetics, biodistribution, and anti-tumor efficacy were evaluated in comparison to the marketed DTX formulation Taxotere. DTX was successfully encapsulated in the hydrophobic micellar core with a high encapsulation efficiency (> 95%) and a high drug loading capacity (4.81 ± 0.08%). DTX-PMs exhibited outstanding stability in the aqueous environment due to the strong interactions between the terminal amino acid residues and docetaxel. The pharmacokinetic study in Sprague-Dawley rats revealed higher DTX concentrations in both whole blood and plasma for the group treated with DTX-PMs than that treated with Taxotere due to the improved stability of the micellar formulation. In human non-small cell lung cancer (A549) tumor-bearing Balb/c nude mice, DTX-PMs significantly improved DTX accumulation and stalled DTX elimination in tumors than in bone marrow. Furthermore, only by half of the DTX dosage, our DTX/mPEG-b-PLA-Phe(Boc) micelles can achieve similar therapeutic effects as Taxotere. Altogether, DTX-PMs hold great promise as a simple and effective drug delivery system for cancer chemotherapy.