In vitro models to predict blood-brain barrier permeability

The design and selection of centrally acting pharmaceuticals is a major challenge for drug delivery to the brain. This review discusses the use of physicochemical parameters and cell culture models to predict blood-brain barrier permeability. Physicochemical parameters have been successfully used to predict blood-brain barrier penetration of molecules that exhibit passive transport and that do not affect junctional permeability, are not transported by a carrier or receptor and are not subject to metabolism or apical recycling. In vitro cell culture models use the brain microvessel endothelial cells that constitute the blood-brain barrier in vivo. Although these cells undergo some de-differentiation in culture, primary endothelial cultures have been shown to maintain several morphological, biochemical and functional properties of the blood-brain barrier in vivo. Bovine brain microvessel endothelial cell systems have been successfully used to generate in vitro/in vivo correlations. These endothelial cell culture models can also be used to study transport mechanisms. This information can be utilized in the design of compounds that either penetrate into or are excluded from the brain.