Case study: adapting in vitro blood–brain barrier models for use in early-stage drug discovery

Abstract

Several parameters influencing the brain distribution of compounds must be considered when designing potential neuropharmaceuticals in early-stage drug discovery. The blood-brain barrier (BBB) represents an obstacle for drug penetration into the brain. Many in vitro BBB models have proven useful for predicting the BBB permeation rate, but do not meet all criteria for use in early-stage drug discovery: feasibility, rapidity, reliability and a low requirement for human resources. To meet this demand, we have developed a robust, higher-throughput, cell-based model exhibiting BBB features (low paracellular permeability, functional efflux pumps and the correct endothelial phenotype). This system comes in a ready-to-use, frozen format, appropriate for in-house use by large pharmaceutical firms and small biotech companies during early-stage drug discovery.