ReviewKeynoteIn vitro blood-brain barrier models for drug research: state-of-the-art and new perspectives on reconstituting these models on artificial basement membrane platforms

•Drug penetration through the BBB is a major challenge for treating CNS diseases.•In vitro BBB models are invaluable for evaluating drug transport into the brain.•Benefits and limitations of in vitro BBB models in drug research are discussed.•Contribution of extracellular cell culture matrix is generally ignored.•New outlook on reconstituting BBB models on artificial basement membrane platform.

In vitro blood-brain barrier (BBB) models are indispensable screening tools for obtaining early information about the brain-penetrating behaviour of promising drug candidates. Until now, in vitro BBB models have focused on investigating the interplay among cellular components of neurovascular units and the effect of fluidic sheer stress in sustaining normal BBB phenotype and functions. However, an area that has received less recognition is the role of the noncellular basement membrane (BM) in modulating BBB physiology. This review describes the state-of-the-art on in vitro BBB models relevant in drug discovery research and highlights their strengths, weaknesses and the utility potential of some of these models in testing the permeability of nanocarriers as vectors for delivering therapeutics to the brain. Importantly, our review also introduces a new concept of engineering artificial BM platforms for reconstituting BBB models in vitro.