The Role of Plasma Protein Binding in Drug Delivery to Brain

Many factors influence drug activity in brain. One of the most important is the ability of a drug to gain access to brain following systemic administration by passage across the blood-brain barrier (BBB). The BBB is formed at the cerebral capillaries by a continuous layer of endothelial cells that are joined together by high resistance tight junctions (Pardridge, 1998). These tight junctions effectively seal off the aqueous paracellular channels between brain endothelial cells, so that if a drug is to gain access to brain it must either be of the appropriate lipid solubility, hydrogen bonding capacity, and size to readily dissolve and diffuse across the lipophilic endothelial cell membranes (Habgood et al.,2000) or be transported across the endothelium by any of 20 or more active or facilitated carrier systems which are expressed in brain capillaries at high levels (Smith et al.,1995).