Delivery of therapeutic agents to the central nervous system: the problems and the possibilities

The presence of a blood-brain barrier (BBB) and a blood-cerebrospinal fluid barrier presents a huge challenge for effective delivery of therapeutics to the central nervous system (CNS). Many potential drugs, which are effective at their site of action, have failed and have been discarded during their development for clinical use due to a failure to deliver them in sufficient quantity to the CNS. In consequence, many diseases of the CNS are undertreated. In recent years, it has become clear that the blood-CNS barriers are not only anatomical barriers to the free movement of solutes between blood and brain but also transport and metabolic barriers. The cell association, sometimes called the neurovascular unit, constitutes the BBB and is now appreciated to be a complex group of interacting cells, which in combination induce the formation of a BBB. The various strategies available and under development for enhancing drug delivery to the CNS are reviewed.(C) 2004 Elsevier Inc. All rights reserved.