Paclitaxel-loaded PEGylated PLGA-based nanoparticles: In vitro and in vivo evaluation

被引:503
作者
Danhier, Fabienne [1 ]
Lecouturier, Nathalie [1 ]
Vroman, Benoit [1 ]
Jerome, Christine [2 ]
Marchand-Brynaert, Jacqueline [3 ]
Feron, Olivier [4 ]
Preat, Veronique [1 ]
机构
[1] Catholic Univ Louvain, Unite Pharm Galen, B-1200 Brussels, Belgium
[2] Univ Liege, Ctr Etud & Rech Macromol, B-4000 Liege, Belgium
[3] Catholic Univ Louvain, Unite Chim Organ & Med, B-1348 Louvain, Belgium
[4] Catholic Univ Louvain, Lab Pharmacol & Therapeut FATH5349, B-1200 Brussels, Belgium
关键词
Paclitaxel; PEGylated nanoparticle; PLGA; Anti-tumoral activity; CELLULAR UPTAKE; PARTICLE-SIZE; CREMOPHOR-EL; TAXOL(R); PHARMACOKINETICS; PHOSPHORYLATION; EFFICIENCY; POLYMERS; DELIVERY; RELEASE;
D O I
10.1016/j.jconrel.2008.09.086
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The purpose of this study was to develop Cremophor (R) EL-free nanoparticles loaded with Paclitaxel (M), intended to be intravenously administered, able to improve the therapeutic index of the drug and devoid of the adverse effects of Cremophor (R) EL. PTX-loaded PEGylated PLGA-based were prepared by simple emulsion and nanoprecipitation. The incorporation efficiency of PTX was higher with the nano precipitation technique. The release behavior of PTX exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous release. The in vitro anti-tumoral activity was assessed using the Human Cervix Carcinoma cells (HeLa) by the MTT test and was compared to the commercial formulation Taxol (R) and to Cremophor (R) EL When exposed to 25 mu g/ml of M, the cell viability was lower for M-loaded nanoparticles than for Taxol (R) (IC50 5.5 vs 15.5 mu g/ml). Flow cytometry studies showed that the cellular uptake of PTX-loaded nanoparticles was concentration and time dependent. Exposure of HeLa cells to Taxol (R) and M-loaded nanoparticles induced the same percentage of apoptotic cells. M-loaded nanoparticles showed greater tumor growth inhibition effect in vivo on TLT tumor, compared with Taxol (R) Therefore, M-loaded nanoparticles may be considered as an effective anticancer drug delivery system for cancer chemotherapy. (C) 2008 Published by Elsevier B.V.
引用
收藏
页码:11 / 17
页数:7
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