Preface [Hot Topic: Blood-Brain Barrier (Executive Editor: William A. Banks)]

This issue of Current Pharmaceutical Design is dedicated to delivery of therapeutics to the central nervous system (CNS). Some of the most devastating diseases facing mankind are those of the CNS. A great number of substances are candidates for treatment of CNS diseases, but therapeutic development in this area faces a special challenge: the blood-brain barrier (BBB). Almost as great as the actual BBB, is the barrier of knowledge, as right perceptions and wrong perceptions about the BBB battle each other in the minds of those interested in drug delivery. Here, we present 6 reviews by eminent BBB researchers. Their reviews cover much traditional ground, but more importantly, offer fresh insights into the mysteries of the BBB. The first article by David J. Begley is a most timely review about one of the hottest area in BBB [1]. The ABC transporters include the efflux systems of the multi-drug resistance and p-glycoprotein families. This area has developed rapidly and independently in many different fields. Dr. Begley's article clarifies terminology, anatomical locations, and function. It also offers brilliant insights on the topics of efflux and of BBB in general. One area in which efflux has been shown to be of particular importance is that of treatment of AIDS, especially neuroAIDS. Most HIV-1 antivirals are transported out of the brain, creating a reservoir for virus. Dr. Sarah A. Thomas has written a wonderful review of this area [2]. This article, in combination with that of Begley's, give insight into the great role which BBB efflux systems will play in CNS therapeutics. One of the most promising groups of potential CNS therapeutics is that of the VIP / PACAP / Secretin family. This family is comprised of peptides which have a great number of CNS effects, including that of acting as powerful neurotrophins. Unlike most peptides or regulatory proteins, we know a great deal about how these peptides cross the BBB and their effects once in the CNS. Ak et al review this topic thoroughly in a format that could act as a roadmap for work on other families of peptides and regulatory proteins [3]. The review by Rautio and Chikhale addresses one of the special areas of therapeutic delivery across the BBB, that of treatment of brain tumors [4]. A number of new and novel approaches are being investigated which deal with the BBB in a variety of ways. The review by Kabanov and Batrakova [5] addresses similar issues to drug delivery, but across the normal BBB. This review addresses three relatively new approaches to drug delivery based on fundamental principles, such as negating efflux, of BBB drug delivery. Finally, a review by William A. Banks of a more speculative nature raises the question of whether the extracellular pathways may be useful for delivery of therapeutics [5]. Two candidate therapeutics, antibodies directed against amyloid beta protein for use in Alzheimer's disease and erythropoietin used in treatment of strokes, likely enter the brain by this mechanism. Overall, this issue addresses important aspects of therapeutic delivery across the BBB. I thank the contributors for their hard work and excellent reviews.