The expected characteristics of an in vitro human Blood Brain Barrier model derived from cell lines, for studying how ABC transporters influence drug permeability

Abstract

The interface between the Central Nervous System (CNS) and the blood, known as the Blood Brain Barrier (BBB), must possess highly effective mechanisms for facilitating the transport of specific nutrients and limiting the transport of xenobiotics. The endothelial cells are major constituents of the BBB; they are characterized by tight junctions and the presence of the ATP Binding Cassette (ABC) transporter family. These transporters regulate the exit of compounds from the endothelial cells. An understanding of how these compounds could interact with the ABC transporters expressed at the BBB, could play a key role in drug research and development. Currently, there is neither a standard BBB pharmacological model nor a method for studying drug permeability and ABC transporter interactions. A pharmacological model must be available, quick to implement and inexpensive.The main parameters useful for evaluating the interaction of the BBB with ABC transporters are bilateral studies and the efflux ratio determination. These parameters could be influenced by different parameters, such as cell lines, apparent permeability, choice of inserts, and other parameters, which would be detailed in this review.