In vitro models of the blood-brain barrier for the study of drug delivery to the brain.

Wilhelm, Imola Mária and Krizbai, István Adorján (2014) In vitro models of the blood-brain barrier for the study of drug delivery to the brain. MOLECULAR PHARMACEUTICS, 11 (7). ISSN 1543-8384

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Abstract

The most important obstacle to the drug delivery into the brain is the presence of the blood-brain barrier, which limits the traffic of substances between the blood and the nervous tissue. Therefore, adequate in vitro models need to be developed in order to characterize the penetration properties of drug candidates into the central nervous system. This review article summarizes the presently used and the most promising in vitro BBB models based on the culture of brain endothelial cells. Robust models can be obtained using primary porcine brain endothelial cells and rodent co-culture models, which have low paracellular permeability and express functional efflux transporters, showing good correlation of drug penetration data with in vivo results. Models mimicking the in vivo anatomo-physiological complexity of the BBB are also available, including triple co-culture (culture of brain endothelial cells in the presence of pericytes and astrocytes), dynamic and microfluidic models; however, these are not suitable for rapid, high throughput studies. Potent human cell lines would be needed for easily available and reproducible models which avoid interspecies differences.

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