In Vitro and Ex Vivo Model Systems to Measure ABC Transporter Activity at the Blood-Brain Barrier

Author(s): Nienke M. de Wit, Gijs Kooij, Helga E. de Vries

Journal Name: Current Pharmaceutical Design

Volume 22 , Issue 38 , 2016

Become EABM
Become Reviewer
Call for Editor


With the aging population the occurrence of central nervous system diseases such as cancer, mental disorders and neurodegenerative diseases, is expected to increase and hence, the demand for effective drugs. However, the passage of drugs across the blood-brain barrier represents a major challenge in accomplishing efficient brain delivery of therapeutic agents. This highly efficient barrier is composed of a monolayer of capillary endothelial cells supported by pericytes and astrocytic end-feet, that together effectively shield the brain from the blood. The brain microvascular endothelial cells form a physical and metabolic barrier where paracellular and transcellular transport of molecules in and out of the brain is closely regulated, allowing nutrients to pass but preventing the entry of harmful neurotoxic substances, including drugs. For this purpose brain endothelial cells express efficient efflux pumps, such as ATP binding cassette (ABC) transporters, which limit the delivery of drugs into the brain. To treat the above-mentioned chronic central nervous system disorders, it is crucial to design compounds that can pass the blood-brain barrier and thus the ABC transporters. In order to achieve this, representative models of the blood-brain barrier with predictive validity are necessary. This review discusses the current in vitro and ex vivo model systems that are used to measure ABC transporter activity in order to study potential in vivo efficacy of blood-brain barrier-drug passage.

Keywords: Blood-brain barrier, ABC transporters, drug delivery, P-glycoprotein, breast cancer resistant protein, central nervous system diseases.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2016
Published on: 29 November, 2016
Page: [5768 - 5773]
Pages: 6
DOI: 10.2174/1381612822666160810145536
Price: $65

Article Metrics

PDF: 38
PRC: 1