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®. 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 Taxol® after 24, 48, 72 h culture at the same drug concentration of 1 μg/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-under-the-curve (AUC0−∞), 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® with 10 mg/kg dose i.v. injection. The half-life (t1/2) 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®. The distribution volume at steady state for the drug loaded in the NPs was 7.21±2.17 l/kg, which was 2.93 times of 2.46±1.41 l/kg for Taxol®. 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.