Drug Transfer Across the Blood-Brain Barrier: Correlation Between in Vitro and in Vivo Models
To provide an in vitro system for studying brain capillary functions, we have developed a process of co-culture that closely mimics the in vivo situation, by culturing brain capillary endothelial cells on one side of a filter and astrocytes on the other. In these conditions, endothelial cells retain all the endothelial cell markers and the characteristics of the blood-brain barrier. To validate our in vitro blood-brain barrier model, we have compared the transport of ten different compounds across the in vitro model vs. transport across the blood-brain barrier in vivo. In vivo brain extraction (Eo) are measured according to the method of Oldendorf. The in vivo and in vitro Eo values show a strong correlation as indicated by the Spearman’s co-efficient (r = 0.88, p < 0.01). The in vitro blood-brain barrier permeability for glucose and leucine i.e. compounds that traverse the blood-brain barrier via carrier mediation is in the same range as the blood-brain barrier permeability in vivo indicating that in our model the glucose and leucine transporters are always present. The relative ease with which such co-cultures can be produced in large quantities would facilitate the investigations in delivery of nutriments across the blood-brain barrier, and the screening of new centrally acting drugs.