Introduction

The ability to permeate across the blood–brain barrier (BBB) is essential for drugs acting on the central nervous system (CNS), whereas for peripherally acting drugs negligible penetration across the BBB is preferable to avoid CNS side-effects. Transfers of compounds from the circulating blood into the brain interstitial fluid are strictly regulated by the function of brain capillary endothelial cells, which are lined by tight intercellular junctions, lacking fenestrae, and make up the BBB in vivo.

This chapter summarizes the mechanisms regulating the influx and efflux processes of drugs, including large peptides, at the BBB in order to understand the net drug transport into the brain, and describes possible strategies to regulate drug entry into the brain, not by lipid-mediated transport, but by utilizing specific transport systems expressed at the brain capillary endothelial cell membrane. This is not intended to be a comprehensive review of the literature on drug delivery into the brain: readers are referred to recent review articles for more detailed information (Cornford, 1985; Pardridge, 1991, 1995a,b; Banks et al., 1992; Terasaki and Tsuji, 1994, 1995; Bergley, 1996; Border and Prokai, 1995; Zlokovic, 1995; Tamai and Tsuji, 1996; Tsuji and Tamai, 1997).