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Enhanced anti-glioblastoma efficacy by PTX-loaded PEGylated poly(ɛ-caprolactone) nanoparticles: In vitro and in vivo evaluation

2010; Elsevier BV; Volume: 402; Issue: 1-2 Linguagem: Inglês

10.1016/j.ijpharm.2010.10.005

1873-3476

Hongliang Xin, Liangcen Chen, Jijin Gu, Xiaoqing Ren, Zhang wei, Jieqi Luo, Yanzuo Chen, Xinyi Jiang, Xianyi Sha, Xiaoling Fang,

Nanoplatforms for cancer theranostics

The aim of this work was to investigate the anti-tumor effect of paclitaxel (PTX)-loaded methoxy poly(ethylene glycol)-poly(ɛ-caprolactone) nanoparticles (MPEG-NP/PTX) against glioblastoma multiforme (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 °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(ɛ-caprolactone) conventional nanoparticles (NP/PTX). 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(ɛ-caprolactone) nanoparticles (MPEG-NP) displayed much stronger fluorescence signal and 3-fold larger Area-Under-Curve (AUC) than poly(ɛ-caprolactone) conventional nanoparticles (NP) in tumor-bearing brain. Furthermore, in vivo anti-glioblastoma effect exhibited the mean survive time of MPEG-NP/PTX (28 days) was much longer than those of Taxol injection (20 days) and NP/PTX (23 days). Therefore, MPEGylated poly(ɛ-caprolactone) nanoparticles significantly enhanced the anti-glioblastoma activity of PTX and might be considered a promising drug delivery system against advanced glioblastoma.