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+/-21nm 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 Taxol((R)) after 24, 48, 72h culture at the same drug concentration of 1microg/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 (AUC(0-infinity)), which determines the therapeutic effects of a dose, was found to be 29,600+/-1,690ng-h/ml for the NP formulation, which is 3.09 times of 9,570+/-1,480ng-h/l for Taxol((R)) with 10mg/kg dose i.v. injection. The half-life (t(1/2)) of the drug formulated in the NPs was found to be 18.80+/-3.14h, which is 2.75 times of 6.84+/-1.39h for Taxol((R)). The distribution volume at steady state for the drug loaded in the NPs was 7.21+/-2.17l/kg, which was 2.93 times of 2.46+/-1.41l/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.
Dong
Yuancai
Y
Department of Chemical and Biomolecular Engineering, National University of Singapore, Block E5, 02-11, 4 Engineering Drive 4, Singapore 117576, Singapore.
Feng
Si-Shen
SS
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D008297:Male; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D011091:Polyesters; D011092:Polyethylene Glycols; C033616:poly(lactide); D017239:Paclitaxel