In vitro and in vivo evaluation of methoxy polyethylene glycol-polylactide (MPEG-PLA) nanoparticles for small-molecule drug chemotherapy

Methoxy polyethylene glycol-polylactide (MPEG-PLA) nanoparticles (NPs) were prepared by the nanoprecipitation method with particle size of 140 +/- 21 nm in diameter and drug encapsulation efficiency of 87.6 +/- 3.1 %. In vitro cytotoxicity of the drug formulated in the NPs was investigated with MCF-7 cancer cells in close comparison with that of Taxol((R))). The in vitro cytotoxicity with MCF-7 cells showed that the NP formulation could be 33.3, 10.7, 7.7 times more effective than Taxolc((R)) after 24, 48, 72h culture at the same drug concentration of I mu g/ml. Confocal laser scanning microscopy (CLSM) visualized cellular internalization of the coumarin 6-loaded MPEG-PLA NPs. The in vitro results were further confirmed by the in vivo pharmacokinetic analysis with SD rats. The total area-underthe-curve (AUC(0-infinity)), which determines the therapeutic effects of a dose, was found to be 29,600 +/- 1690 ng-h/ml for the NP formulation, which is 3.09 times of 9570 +/- 1480 ng-h/l for Taxol((R)) with 10 mg/kg dose i.v. injection. The half-life (t(1/2)) of the drug formulated in the NPs was found to be 18.80 +/- 3.14 h, which is 2.75 times of 6.84 +/- 1.39 h for Taxol((R)). The distribution volume at steady state for the drug loaded in the NPs was 7.21 +/- 2.171/kg, which was 2.93 times of 2.46 +/- 1.411/kg for Taxol((R)). Our proof-of-concept in vitro and in vivo valuation shows that our MPEG-PLA NP formulation could have great advantages versus the original drug in small-molecule drug chemotherapy as well as in various applications in nanomedicine. (c) 2007 Elsevier Ltd. All rights reserved.