The synergic antitumor effects of paclitaxel and temozolomide co-loaded in mPEG-PLGA nanoparticles on glioblastoma cells.

Yuanyuan Xu,Yiming Li,Yourong Duan,Yanwei Teng,Ying Sun,Yi Wang,Ming Shen

doi:10.18632/oncotarget.7896

Yuanyuan Xu, Yiming Li + Show 5 more

Open Access

https://doi.org/10.18632/oncotarget.7896

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Journal: Oncotarget	Publication Date: Mar 3, 2016
Citations: 54	License type: cc-by

Affiliation: Shanghai Jiao Tong University, Huashan Hospital

Abstract

To get better chemotherapy efficacy, the optimal synergic effect of Paclitaxel (PTX) and Temozolomide (TMZ) on glioblastoma cells lines was investigated. A dual drug-loaded delivery system based on mPEG-PLGA nanoparticles (NPs) was developed to potentiate chemotherapy efficacy for glioblastoma. PTX/TMZ-NPs were prepared with double emulsification solvent evaporation method and exhibited a relatively uniform diameter of 206.3 ± 14.7 nm. The NPs showed sustained release character. Cytotoxicity assays showed the best synergistic effects were achieved when the weight ratios of PTX to TMZ were 1:5 and 1:100 on U87 and C6 cells, respectively. PTX/TMZ-NPs showed better inhibition effect to U87 and C6 cells than single drug NPs or free drugs mixture. PTX/TMZ-NPs (PTX: TMZ was 1:5(w/w)) significantly inhibited the tumor growth in the subcutaneous U87 mice model. These results indicate that coordinate administration of PTX and TMZ combined with NPs is an efficient method for glioblastoma.

Highlights

Glioblastoma (GBM) is the most common and aggressive primary brain tumor [1, 2] with median survivals only 12-15 months [3, 4]
The accumulated amount of PTX released from PTX solution achieved the maximum at 20 h, while from PTX-NPs or PTX/TMZ-NPs were both near 80 h (Figure 1C), showing apparent sustained characteristic and no significant difference between the two nanoparticles groups
The TMZ released from the TMZNPs and PTX/TMZ-NPs showed remarkable sustained feature comparing with TMZ solution (Figure 1D)

Summary

Introduction

Glioblastoma (GBM) is the most common and aggressive primary brain tumor [1, 2] with median survivals only 12-15 months [3, 4]. The present treatment of GBM is multimodal involving surgery, radiotherapy and chemotherapy [5]. Temozolomide (TMZ) is the first agent in 20 years approved by the FDA to treat glioblastoma and has been one of the most commonly used anti-glioma agents with limited adverse effects [6, 7] due to its ability penetrating the blood brain barrier (BBB). The standard treatment is maximal surgical resection and maintenance treatment with temozolomide (TMZ), which could improve median and 5-year survival significantly [8]. Thereby, combinational administrations of TMZ with other chemotherapeutics have been under study for improving the efficacy of glioblastoma therapies [12]

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