Blood-brain barrier models: Rationale for selection.

Brain delivery is a broad research area, the outcomes of which are far hindered by the limited permeability of the blood-brain barrier (BBB). Over the last century, research has been revealing the BBB complexity and the crosstalk between its cellular and molecular components. Pathologically, BBB alterations may precede as well as be concomitant or lead to brain diseases. To simulate the BBB and investigate options for drug delivery, several in vitro, in vivo, ex vivo, in situ and in silico models are used. Hundreds of drug delivery vehicles successfully pass preclinical trials but fail in clinical settings. Inadequate selection of BBB models is believed to remarkably impact the data reliability leading to unsatisfactory results in clinical trials. In this review, we suggest a rationale for BBB model selection with respect to the addressed research question and downstream applications. The essential considerations of an optimal BBB model are discussed.