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  • Title: Cytotoxicity of paclitaxel incorporated in PLGA nanoparticles on hypoxic human tumor cells.
    Author: Jin C, Bai L, Wu H, Song W, Guo G, Dou K.
    Journal: Pharm Res; 2009 Jul; 26(7):1776-84. PubMed ID: 19384463.
    Abstract:
    PURPOSE: The aim of this work was to prepare paclitaxel-loaded PLGA nanoparticles and determine cytotoxicity of released paclitaxel for two hypoxic human tumor cell lines: breast carcinoma (MCF-7) and carcinoma cervicis (HeLa). METHODS: Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing paclitaxel were prepared by o/w emulsification-solvent evaporation method. Physicochemical characteristics of nanoparticles were studied. Cellular uptake of nanoparticles was evaluated by transmission electronic microscopy and fluorescence microscopy. Flow cytometry quantified the number of cells held in G(2)/M phase. Cell viability was determined by the ability of single cell to form colonies. Biodistribution of nanoparticles in mice was evaluated by fluorescence microscopy. RESULTS: The nanoparticles were spherical with average diameter 318 +/- 5.1 nm. The encapsulation efficiency was 88.52%. The drug release profile in vitro exhibited a biphasic pattern. Cellular uptake was observed. Co-culture of tumor cells with paclitaxel-loaded nanoparticles demonstrated that released paclitaxel retained its bioactivity to block cells in G(2)/M phase. Paclitaxel-loaded nanoparticles exhibited cytotoxic effect on both hypoxic MCF-7 and HeLa cells and its cytotoxicity was more significant than that of free paclitaxel. Fluorescent nanoparticles were mainly distributed to liver and spleen of mice. CONCLUSIONS: Paclitaxel-loaded PLGA nanoparticles may be considered a promising drug delivery system to eradicate hypoxic tumor cells.
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