Abstract
Restriction of drug distribution into the brain by the blood-brain barrier (BBB) is one of the serious issues for DDS. Recent progress in the BBB research has revealed that various transport systems function at the BBB, such as blood-to-brain influx transport and brain-to-blood efflux transport. The blood-to-brain influx transport system facilitates drug permeability across the BBB, such as System L transport for levodopa, while the brain-to-blood efflux transport prevents entry of drug into the brain. Therefore, the way of recognition by BBB transport systems makes important contribution to drug distribution into the brain. Furthermore, using the receptor-mediated transport system at the BBB, non-viral carrier for the DDS to the brain has been reported. This non-viral carrier has succeeded to deliver plasmid DNA and siRNA into the brain. In vitro BBB model is an important technology for estimating BBB permeability of drugs. We have established conditionally immortalized brain capillary endothelial cells from transgenic rats and mice. The BBB permeability of compounds estimated from the uptake study using these cell lines had good correlation to the BBB permeability reported in vivo. The progress in the BBB research provided us important knowledge to understand drug distribution and delivery into the brain.
