Consideration for future in vitro BBB models - technical development to investigate the drug delivery to the CNS

Abstract

Blood vessels in the central nervous system (CNS) limit the material exchange between blood and parenchyma by blood brain barrier (BBB). At present, no appropriate in vitro BBB models are available for the investigation whether or not the candidate compounds for new drugs could be delivered to the CNS. This causes huge difficulties of the development of CNS drugs and prediction of CNS adverse effects. In this review, I first outline the structures and functions of BBB, together with the parameters used for the quantification of BBB functions. I also introduce the history of in vitro BBB models used in the drug development so far, i.e., the transition from non-cell models to the models using primary culture of rodent cells, porcine, bovine, cell lines, etc. More recently, the application of human cells differentiated from human induced pluripotent stem cells and microfluidic engineering have already started. BBB is essential for the maintenance of brain homeostasis and the mechanisms of the BBB development will be clarified by reproducing functional BBB on the dish. The new in vitro models and the data may provide accurate prediction of drug delivery to the CNS and the improvement of the evaluation system for toxicity and safety, thereby leading to successful launch of new drugs on the market.