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

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 cytoto...

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Veröffentlicht in:Journal of controlled release 2019-09, Vol.309, p.72-81
Hauptverfasser: Zhao, Mengnan, Bozzato, Elia, Joudiou, Nicolas, Ghiassinejad, Sina, Danhier, Fabienne, Gallez, Bernard, Préat, Véronique
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •A paclitaxel and temozolomide coloaded hydrogel was developed to treat glioblastoma.•Paclitaxel and temozolomide synergistically inhibited U87MG colony formation.•Paclitaxel had sustained release through hydrogel for at least 1 month in mice brains.•Temozolomide did not up-regulate O6-methylguanine-DNA methyltransferase expression.•The drug combination suppressed tumor growth more efficiently than the single drugs.
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2019.07.015