Recent progress in blood–brain barrier and blood–CSF barrier transport research: Pharmaceutical relevance for drug delivery to the brain

The blood–brain barrier (BBB) and the blood–CSF barrier (BCSFB) possess multiple transport systems for endogenous and xenobiotic compounds to maintain functional homeostasis in the central nervous system (CNS). Accumulating evidence on the transport systems has provided a basis for the development of rational strategies for drug delivery and targeting to CNS. The blood-to-brain influx transport systems at the BBB have a great potential for CNS-acting drug delivery and targeting to the brain. The brain-to-blood efflux transport systems at the BBB including ATP-binding cassette transporters hinder the drug penetration to the brain. Efflux transport systems at the BBB and BCSFB also play an important role in cerebral clearance of endogenous neurotoxic compounds which are associated with disorders of the CNS. Several drugs influence the endogenous clearance system at the brain barriers. This chapter focuses on the current state of knowledge concerning the roles of transport systems for endogenous and xenobiotic compounds at the BBB and the BCSFB, and the potential implications of these systems for CNS drug delivery.