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Review
. 2020 Nov;34(11):1121-1131.
doi: 10.1007/s40263-020-00766-w. Epub 2020 Sep 23.

Overview of Current Drug Delivery Methods Across the Blood-Brain Barrier for the Treatment of Primary Brain Tumors

Rianne Haumann  1   2 , Jessica Carvalho Videira  1   2 , Gertjan J L Kaspers  1   2 , Dannis G van Vuurden  1   2 , Esther Hulleman  3   4
Affiliations
Review

Overview of Current Drug Delivery Methods Across the Blood-Brain Barrier for the Treatment of Primary Brain Tumors

Rianne Haumann et al. CNS Drugs. 2020 Nov.

Abstract

Existing drug delivery methods have not led to a significant increase in survival for patients with malignant primary brain tumors. While the combination of conventional therapies consisting of surgery, radiotherapy, and chemotherapy has improved survival for some types of brain tumors (e.g., WNT medulloblastoma), other types of brain tumors (e.g., glioblastoma and diffuse midline glioma) still have a poor prognosis. The reason for the differences in response can be largely attributed to the blood-brain barrier (BBB), a specialized structure at the microvasculature level that regulates the transport of molecules across the blood vessels into the brain parenchyma. This structure hampers the delivery of most chemotherapeutic agents for the treatment of primary brain tumors. Several drug delivery methods such as nanoparticles, convection enhanced delivery, focused ultrasound, intranasal delivery, and intra-arterial delivery have been developed to overcome the BBB in primary brain tumors. However, prognosis of most primary brain tumors still remains poor. The heterogeneity of the BBB in primary brain tumors and the distinct vasculature of tumors make it difficult to design a drug delivery method that targets the entire tumor. Drug delivery methods that combine strategies such as focused ultrasound and nanoparticles might be a more successful approach. However, more research is needed to optimize and develop new drug delivery techniques to improve survival of patients with primary brain tumors.

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Conflict of interest statement

Rianne Haumann, Jessica Carvalho Videira, Gertjan J.L. Kaspers, Dannis G. van Vuurden, and Esther Hulleman declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Figures

Fig. 1
Fig. 1
Overview of current drug delivery methods for the treatment of primary brain tumors. Panel 1 intranasal drug delivery: drug is formulated in spray particles that enter the brain through the nasal cavity via the neuroepithelium. Here, the drug can enter without interference of the blood–brain barrier (BBB). Panel 2 nanoparticles: nanoparticles encapsulate drugs to increase plasma half-life and allow entry to the brain parenchyma by the enhanced permeability and retention (EPR) effect, endocytosis, and receptor-mediated transcytosis. Panel 3 microbubble-mediated focused ultrasound: microbubbles are intravenously administered and upon the application of focused ultrasound, microbubbles start to oscillate. The oscillation disrupts the BBB, temporarily opening it to allow drugs to enter the brain parenchyma. Panel 4 convection enhanced delivery (CED): surgical placement of catheters in the brain to administer the drug directly in the tumor site. Panel 5 intra-arterial drug delivery: catherization of the blood vessel and injection of drugs directly in the vicinity of the tumor, sometimes in combination with hyperosmolar drugs that open the BBB
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