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

JOURNAL OF CONTROLLED RELEASE

卷:133

Article

Danhier, Fabienne¹  Lecouturier, Nathalie¹  Vroman, Benoit¹  Jerome, Christine²  Marchand-Brynaert, Jacqueline³  Feron, Olivier⁴  Preat, Veronique¹ 

[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;   

DOI  :  10.1016/j.jconrel.2008.09.086

来源: Elsevier

【 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.

【 授权许可】

Free