Preparation, characterization, cytotoxicity and biodistribution of docetaxel-loaded polymeric micelle formulations

Docetaxel-loaded polymeric micelles (PM) were prepared from poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) (PVP-b-PDLLA) using different incorporation methods, additives and drug-loading levels. The in vitro cytotoxicity of docetaxel-loaded PM, the commercial formulation Taxotere, and unloaded vehicles (PVP-b-PDLLA and polysorbate 80) were tested against C26 murine colon and EMT-6 murine mammary tumoral cells. Docetaxel-loaded PM showed comparable in vitro activity to Taxotere, whereas PVP-b-PDLLA was substantially less cytotoxic than polysorbate 80. In vivo toxicity was assessed in mice after intravenous (iv) injections (2 at a 5-day interval) of escalating dose levels of docetaxel-loaded PM or Taxotere. The maximum tolerated dose was reached at 25 mg/kg for both formulations. The acute toxicity of the vehicles was assessed in mice with a single injection of high-dose PVP-b-PDLLA or polysorbate 80. PVP-b-PDLLA was better tolerated than polysorbate 80, even at a 4-fold higher dose. PM formulations and Taxotere were compared in vivo in terms of biodistribution profile and tumor accumulation of docetaxel, but did not show any significant difference. These results reveal that while the in vivo toxicity and biodistribution of docetaxel-loaded PM were similar to those of Taxotere, PVP-b-PDLLA proved to be a safer solubilizer than polysorbate 80.