Blood-Brain Barrier Transport and Drug Targeting to the Brain

Abstract

The transport of drugs to the central nervous system (CNS) from the circulating blood requires them to cross either the blood-brain barrier (BBB) or blood-cerebrospinal fluid barrier (BCSFB) (Fig. 1). The BBB, which is formed by complex tight junctions of brain capillary endothelial cells, separates the circulating blood from the interstitial fluid in the brain. Although the BCSFB is also formed by the complex tight junctions of the choroid plexus epithelial cells and separates the blood from the cerebrospinal fluid (CSF), the area of BBB is about 5,000-times greater than that of the BCSFB. There is an ependymal layer between the brain parenchymal cells and CSF, but this does not act as a barrier to prevent diffusion of drugs from the CSF to the CNS. Nevertheless, the diffusion rate of drugs between CSF and brain parenchymal cells is very slow. Although the cellular volume of the brain capillaries is only 0.1~0.2% of the entire brain, the total length of the brain capillaries is about 600 km and the total surface area is about 9–12 m2 in humans. As the brain capillaries are ramified, like the network in the cerebrum at intervals of about 40 gm, small molecules such as nutrients immediately diffuse into the brain parenchymal ‘cells following their passage across the BBB. In general, the BBB is a main route for drug transport from the blood to the CNS. In other words, a high drug concentration in the CSF is not necessary if the drug is able to cross the BBB very efficiently.