Towards Novel Biomimetic In Vitro Models of the Blood-Brain Barrier for Drug Permeability Evaluation

Current available animal and in vitro cell-based models for studying brain-related pathologies and drug evaluation face several limitations since they are unable to reproduce the unique architecture and physiology of the human blood-brain barrier. Because of that, promising preclinical drug candidates often fail in clinical trials due to their inability to penetrate the blood-brain barrier (BBB). Therefore, novel models that allow us to successfully predict drug permeability through the BBB would accelerate the implementation of much-needed therapies for glioblastoma, Alzheimer's disease, and further disorders. In line with this, organ-on-chip models of the BBB are an interesting alternative to traditional models. These microfluidic models provide the necessary support to recreate the architecture of the BBB and mimic the fluidic conditions of the cerebral microvasculature. Herein, the most recent advances in organ-on-chip models for the BBB are reviewed, focusing on their potential to provide robust and reliable data regarding drug candidate ability to reach the brain parenchyma. We point out recent achievements and challenges to overcome in order to advance in more biomimetic in vitro experimental models based on OOO technology. The minimum requirements that should be met to be considered biomimetic (cellular types, fluid flow, and tissular architecture), and consequently, a solid alternative to in vitro traditional models or animals.