Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 402, Issue 1-2, Pages 238-247Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2010.10.005
Keywords
Polymeric nanoparticles; MPEGylated poly(epsilon-caprolactone); Paclitaxel; Glioblastoma
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Funding
- China 973 program [2007CB935802]
- National Natural Science Foundation of China [30873177]
- National Science and Technology Major Project [2009ZX09310-006]
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The aim of this work was to investigate the anti-tumor effect of paclitaxel (PIX)-loaded methoxy poly(ethylene glycol)-poly(epsilon-caprolactone) nanoparticles (MPEG-NP/PTX) against glioblastoma multi-forme (GBM). MPEG-NP/PTX was prepared by the emulsion and evaporation technique with particle size of 72.5 +/- 2.2 nm and did not change remarkably during the period of 21-day storage at 4 degrees C. The drug-loading coefficient and encapsulation ratio of optimized formulation were 8.2 +/- 0.6% and 90.4 +/- 2.3%, respectively. The in vitro release behavior exhibits a biphase release manner and was affected by PEG segment. In vitro cytotoxicity was assessed using C6 cell lines and was compared to Taxol and PTX-loaded poly(epsilon-caprolactone) conventional nanoparticles (NP/FTX). Cell viability assay against C6 cells exhibited higher or at least comparable cytotoxicity than that of Taxol and NP/PTX More importantly, in vivo real-time fluorescence imaging analysis in intracranial C6 glioblastoma bearing mice showed that the methoxy poly(ethylene glycol)-poly(epsilon-caprolactone) nanoparticles (MPEG-NP) displayed much stronger fluorescence signal and 3-fold larger Area-Under-Curve (AUC) than poly(epsilon-caprolactone) conventional nanoparticles (NP) in tumor-bearing brain. Furthermore, in vivo anti-glioblastoma effect exhibited the mean survive time of MPEG-NP/FTX (28 days) was much longer than those of Taxol injection (20 days) and NP/PTX (23 days). Therefore. MPEGylated poly(epsilon-caprolactone) nanoparticles significantly enhanced the anti-glioblastoma activity of PTX and might be considered a promising drug delivery system against advanced glioblastoma. (C) 2010 Elsevier B.V. All rights reserved.
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