In vitro Models of the Blood-Brain Barrier: Building in physiological complexity

Development of brain therapeutics is significantly hampered by the presence of the blood-brain barrier (BBB). Classical transwell models are able to recapitulate many important aspects of drug transport across the BBB, but are not completely predictive of in vivo brain uptake. Species differences further complicate translation of experimental therapeutics from the benchtop to the clinic. Human BBB models offer some solutions to this problem, and by increasing device complexity both in terms of multicellularity, flow and physical architecture, physiological models of the BBB have been developed that can more faithfully model different aspects of transport and homeostasis BBB. Using these models, it may be possible to improve the predictive capacity in benchmarking candidate therapeutics, and to identify new druggable targets by studying multicellular interactions.