Codelivery of paclitaxel and temozolomide through a photopolymerizable hydrogel prevents glioblastoma recurrence after surgical resection

被引:95
作者
Zhao, Mengnan [1 ]
Bozzato, Elia [1 ]
Joudiou, Nicolas [2 ]
Ghiassinejad, Sina [3 ]
Danhier, Fabienne [1 ]
Gallez, Bernard [4 ]
Preat, Veronique [1 ]
机构
[1] Catholic Univ Louvain, Louvain Drug Res Inst, Adv Drug Delivery & Biomat, Ave Mounier 73,B1-73-12, B-1200 Brussels, Belgium
[2] Catholic Univ Louvain, Louvain Drug Res Inst, NEST, Ave Mounier,B1-73-08, B-1200 Brussels, Belgium
[3] Catholic Univ Louvain, Inst Condensed Matter & Nanosci IMCN, Bio & Soft Matter, Croix Sud 1, B-1348 Brussels, Belgium
[4] Catholic Univ Louvain, Louvain Drug Res Inst, Biomed Magnet Resonance Res Grp, Grp,Ave Mounier 73,B1-73-08, B-1200 Brussels, Belgium
关键词
Glioblastoma; Nanomedicine; Nanoparticles; Local delivery; Hydrogel; Combination therapy; DRUG-DELIVERY; BIODEGRADABLE HYDROGELS; ADJUVANT TEMOZOLOMIDE; UP-REGULATION; GLIOMA-CELLS; PHASE-I; COMBINATION; NANOMEDICINE; RADIOTHERAPY; GEL;
D O I
10.1016/j.jconrel.2019.07.015
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A photopolymerizable hydrogel-based local drug delivery system was developed for the postsurgical treatment of glioblastoma (GBM). We aimed for a local drug combination therapy with paclitaxel (PTX) and temozolomide (TMZ) within a hydrogel to synergistically inhibit tumor growth. The in vitro cytotoxicity of TMZ was assessed in U87MG cells. We demonstrated the synergistic effect of PTX and TMZ on U87MG cells by clonogenic assay. Treatment with TMZ did not induce O6-methylguanine-DNA methyltransferase related drug resistance in tumor-bearing mice. PTX had sustained release for at least 1 month in vivo in healthy mice brains. The drug combination was tolerable and suppressed tumor growth more efficiently than the single drugs in the U87MG orthotopic tumor model. The PTX and TMZ codelivery hydrogel showed superior antitumor effects and can be considered a promising approach for the postsurgical treatment of GBM.
引用
收藏
页码:72 / 81
页数:10
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