Therapeutic effect of cabazitaxel and blood-brain barrier opening in a patient-derived glioblastoma model

Einar Sulheim, Yrr Mørch, Sofie Snipstad, Sven Even Borgos, Hrvoje Miletic, Rolf Bjerkvig, Catharina de Lange Davies, Andreas K.O. Åslund

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

Abstract

Treatment of glioblastoma and other diseases in the brain is especially challenging due to the blood-brain barrier, which effectively protects the brain parenchyma. In this study we show for the first time that cabazitaxel, a semi-synthetic derivative of docetaxel can cross the blood-brain barrier and give a significant therapeutic effect in a patient-derived orthotopic model of glioblastoma. We show that the drug crosses the blood-brain barrier more effectively in the tumor than in the healthy brain due to reduced expression of p-glycoprotein efflux pumps in the vasculature of the tumor. Surprisingly, neither ultrasound-mediated blood-brain barrier opening (sonopermeation) nor drug formulation in polymeric nanoparticles could increase either accumulation of the drug in the brain or therapeutic effect. This indicates that for hydrophobic drugs, sonopermeation of the blood brain barrier might not be sufficient to achieve improved drug delivery. Nonetheless, our study shows that cabazitaxel is a promising drug for the treatment of brain tumors.

Original languageEnglish
Pages (from-to)103-112
Number of pages10
JournalNanotheranostics
Volume3
Issue number1
DOIs
Publication statusPublished - 2019

Keywords

  • Cabazitaxel
  • Glioblastoma
  • Orthotopic model
  • Sonopermeation

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