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Construction of paclitaxel-loaded poly (2-hydroxyethyl methacrylate)-g-poly (lactide)- 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine copolymer nanoparticle delivery system and evaluation of its anticancer activity

Authors Ma X, Wang H, Jin S, Wu Y, Liang XJ

Published Date March 2012 Volume 2012:7 Pages 1313—1328

DOI http://dx.doi.org/10.2147/IJN.S29371

Received 21 December 2011, Accepted 24 January 2012, Published 7 March 2012

Xiaowei Ma*, Huan Wang*, Shubin Jin, Yan Wu, Xing-Jie Liang
Laboratory of Nanomedicine and Nanosafety, Division of Nanomedicine and Nanobiology, National Center for Nanoscience and Technology, People’s Republic of China; and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences, Beijing, People’s Republic of China

*These authors contributed equally to this work

Background: There is an urgent need to develop drug-loaded biocompatible nanoscale packages with improved therapeutic efficacy for effective clinical treatment. To address this need, a novel poly (2-hydroxyethyl methacrylate)-poly (lactide)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine [PHEMA-g-(PLA-DPPE)] copolymer was designed and synthesized to enable these nanoparticles to be pH responsive under pathological conditions.
Methods: The structural properties and thermal stability of the copolymer was measured and confirmed by Fourier transform infrare d spectroscopy, nuclear magnetic resonance, and thermogravimetric analysis. In order to evaluate its feasibility as a drug carrier, paclitaxel-loaded PHEMA-g-(PLA-DPPE) nanoparticles were prepared using the emulsion-solvent evaporation method.
Results: The PHEMA-g-(PLA-DPPE) nanoparticles could be efficiently loaded with paclitaxel and controlled to release the drug gradually and effectively. In vitro release experiments demonstrated that drug release was faster at pH 5.0 than at pH 7.4. The anticancer activity of the PHEMA-g-(PLA-DPPE) nanoparticles was measured in breast cancer MCF-7 cells in vivo and in vitro. In comparison with the free drug, the paclitaxel-loaded PHEMA-g-(PLA-DPPE) nanoparticles could induce more significant tumor regression.
Conclusion: This study indicates that PHEMA-g-(PLA-DPPE) nanoparticles are promising carriers for hydrophobic drugs. This system can passively target cancer tissue and release drugs in a controllable manner, as determined by the pH value of the area in which the drug accumulates.

Keywords: poly (2-hydroxyethyl methacrylate), controlled release, biocompatibility, antitumor activity, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, nanoparticles

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