Novel models for assessing blood-brain barrier drug permeation.

Novel models for assessing blood-brain barrier drug permeation.

Geldenhuys Werner J; Allen David D; Bloomquist Jeffrey R

Expert opinion on drug metabolism & toxicology

2012

2012-06

INTRODUCTION: The blood-brain barrier (BBB) is a selectively permeable micro-vascular unit which prevents many central nervous system (CNS)-targeted compounds from reaching the brain. A significant problem in CNS drug development is the ability to model BBB permeability in a timely, reproducible and cost-effective manner. Through the years, several models have been used such as artificial membranes, cell culture and animal models. AREAS COVERED: In this focused review, the authors cover novel models which have been developed or are in the process of being developed which can be used in modeling BBB. These models can either be used to determine BBB permeability or whether a compound may be disrupting the BBB. Many of these models lend themselves to high-throughput screening. The main model organisms covered here are the grasshopper (Locusta migratoria), fruit fly (Drosophila melanogaster) and zebrafish (Danio rerio). EXPERT OPINION: Many of the models covered here have only recently been utilized for BBB studies and still needs to be fully studied for its impact on reducing costs during drug development. The strength of these models lay in the fact that a whole organism experiment can be done in high throughput fashion as compared with classical vertebrate models such as micro-dialysis.

Humans; Animals; Blood-Brain Barrier/*metabolism; *Capillary Permeability; Drosophila melanogaster/metabolism; Grasshoppers/metabolism; High-Throughput Screening Assays; Pharmaceutical Preparations/*metabolism; Zebrafish/metabolism; Models; Animal

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647–653

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