The efficiency of brain therapeutics is greatly hindered by the blood-brain barrier (BBB). BBB’s protective function, selective permeability, and dynamic functionality maintain the harmony between the brain and peripheral region. Thus, the design of any novel drug carrier system requires the complete study and investigation of BBB permeability, efflux transport, and the effect of associated cellular and non-vascular unit trafficking on BBB penetrability. The in vitro BBB models offer a most promising, and reliable mode of initial investigation of BBB permeability and associated factors as strong evidence for further preclinical and clinical investigation.

This review work covers the structure and functions of BBB components and different types of in vitro BBB models along with factors affecting BBB model development and model selection criteria.

In vivo models assume to reciprocate the physiological environment to the maximum extent. However, the interspecies variability, NVUs trafficking, dynamic behavior of BBB, etc., lead to non-reproducible results. The in vitro models are comparatively less complex, and flexible, as per the study design, could generate substantial evidence and help identify suitable in vivo animal model selection.