Experimental Models of In Vitro Blood–Brain Barrier for CNS Drug Delivery: An Evolutionary Perspective

Central nervous system (CNS) disorders represent one of the leading causes of global health burden. Nonetheless, new therapies approved against these disorders are among the lowest compared to their counterparts. The absence of reliable and efficient in vitro blood–brain barrier (BBB) models resembling in vivo barrier properties stands out as a significant roadblock in developing successful therapy for CNS disorders. Therefore, advancement in the creation of robust and sensitive in vitro BBB models for drug screening might allow us to expedite neurological drug development. This review discusses the major in vitro BBB models developed as of now for exploring the barrier properties of the cerebral vasculature. Our main focus is describing existing in vitro models, including the 2D transwell models covering both single-layer and co-culture models, 3D organoid models, and microfluidic models with their construction, permeability measurement, applications, and limitations. Although microfluidic models are better at recapitulating the in vivo properties of BBB than other models, significant gaps still exist for their use in predicting the performance of neurotherapeutics. However, this comprehensive account of in vitro BBB models can be useful for researchers to create improved models in the future.