Chapter 31. Strategies for Delivery of Drugs Through the Blood-Brain Barrier

Abstract

Listen

Translate article

This chapter discusses some of the recent approaches that have been used to circumvent the blood-brain barrier (BBB). There are two barrier systems in brain, the BBB and the blood-CSF barrier. Because of the presence of the BBB, that acts as a system-wide cellular membrane separating blood and brain interstitial space, hydrophilic drugs that readily gain access to other tissues are barred from entry into the brain. The most common invasive procedure for drug delivery to the central nervous system (CNS) is the implantation of a catheter into the ventricular system for the delivery of drugs directly to brain, bypassing the BBB. A powerful pharmacologic-based approach for drug delivery to brain is drug latentiation or the conversion of hydrophilic drugs into lipid-soluble drugs. One of the most novel recent approaches to the delivery of drugs across the BBB is the work of Bodor and colleagues. Their concept, called “chemical delivery systems,” is based on a dihydropyridinepyridinium salt redox system. Additional strategies for the delivery of drugs to the brain arise from an understanding of the basic physiology of transport processes at the BBB for nutrients and peptides. The presence of specific peptide receptor transport systems in the BBB suggests a new strategy for peptide delivery to the brain. Moreover, a convenient in vitro model system for BBB peptide transport is now available, using isolated human brain capillaries, and this approach allows for rapid screening of the novel chimeric peptides for transport through the BBB in vivo in man. Although much work needs to be done in this field, it becomes clear that an understanding of the basic physiology of BBB transport processes may lead to new strategies for the delivery of pharmaceuticals to the brain.