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Nanotheranostics. 2019 Feb 7;3(1):103-112. doi: 10.7150/ntno.31479. eCollection 2019.

Therapeutic Effect of Cabazitaxel and Blood-Brain Barrier opening in a Patient-Derived Glioblastoma Model.

Author information

1
Department of Physics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
2
Department of Biotechnology and Nanomedicine, SINTEF AS, Trondheim Norway.
3
Cancer Clinic, St.Olav's University Hospital, Trondheim Norway.
4
Department of Pathology, Haukeland University Hospital, Bergen, Norway.
5
Department of Biomedicine, University of Bergen, Norway.
6
Department of Oncology, Luxembourg Institute of Health, Luxembourg.
7
Stroke Unit, Department of internal medicine, St. Olav's University Hospital, Trondheim, Norway.

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.

KEYWORDS:

cabazitaxel; glioblastoma; orthotopic model; sonopermeation

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

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