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

Authors :
Sina Ghiassinejad
Elia Bozzato
Bernard Gallez
Véronique Préat
Nicolas Joudiou
Mengnan Zhao
Fabienne Danhier
UCL - SSS/LDRI/MCPB - Analyse clinique par spectrométrie de masse de métabolites et de composés d'intérêts pharmaceutique et biologique
UCL - SSS/LDRI - Louvain Drug Research Institute
UCL - SST/IMCN/BSMA - Bio and soft matter
Source :
Journal of controlled release, Vol. 309, p. 72-81 (2019)
Publication Year :
2019

Abstract

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.

Details

ISSN :
18734995
Volume :
309
Database :
OpenAIRE
Journal :
Journal of controlled release : official journal of the Controlled Release Society
Accession number :
edsair.doi.dedup.....b8fc3d487ef77864f57267c12773c932