Journal Article

From blood–brain barrier to blood–brain interface: new opportunities for CNS drug delivery

Banks, William A.

2016

Overview

Key Points The blood–brain barriers (BBBs) are dynamic, adaptable, interactive monolayers of cells, including endothelial, ependymal and tanycytic cells, that participate in central nervous system (CNS) protection, are responsible for CNS nutrition and homeostasis, and facilitate serum-based brain–body communications. The cells forming the BBB are in communication with other cells of the CNS, thus forming the neurovascular unit. This communication informs the BBB of the needs of the CNS, allowing it to adapt to the needs of the CNS. The BBB also communicates with circulating immune cells and via blood-borne signals with the peripheral tissues. Through transport, secretion and other mechanisms, the BBB relays information between the periphery and the CNS. The complexity of the BBB complicates CNS drug delivery, but also provides many unique opportunities for drug delivery. Manipulation of transporters, secretory functions, the extracellular pathways, and adsorptive transcytosis are examples of promising approaches to drug development. The complexity of the BBB predisposes it to dysfunctions that can result in or promote disease. Such dysfunctions include BBB disruption as well as dysfunctions related to BBB transporters, neurovascular unit communication and secretion. Thus, the BBB itself can be a therapeutic target. Research on the blood–brain barrier (BBB) has led to the concept of a complex, dynamic interface between the central nervous system (CNS) and periphery. Banks considers how this new understanding can combine with classical concepts to inform CNS drug delivery strategies and promote BBB integrity in various diseases. One of the biggest challenges in the development of therapeutics for central nervous system (CNS) disorders is achieving sufficient blood–brain barrier (BBB) penetration. Research in the past few decades has revealed that the BBB is not only a substantial barrier for drug delivery to the CNS but also a complex, dynamic interface that adapts to the needs of the CNS, responds to physiological changes, and is affected by and can even promote disease. This complexity confounds simple strategies for drug delivery to the CNS, but provides a wealth of opportunities and approaches for drug development. Here, I review some of the most important areas that have recently redefined the BBB and discuss how they can be applied to the development of CNS therapeutics.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/378/1341 / 692/308/153 / 692/617/375/1666 / 692/617/375/365/1283 / 692/700/565/1436/152 / Analysis / Biological Transport - drug effects / Biomedicine / Biotechnology / Blood-brain barrier / Blood-Brain Barrier - drug effects / Blood-Brain Barrier - metabolism / Blood-Brain Barrier - physiopathology / Cancer Research / Care and treatment / Central Nervous System Agents - pharmacology / Central nervous system diseases / Central Nervous System Diseases - drug therapy / Central Nervous System Diseases - metabolism / Central Nervous System Diseases - physiopathology / Drug delivery systems / Drug Delivery Systems - methods / Drugs / Humans / Medication Therapy Management / Medicinal Chemistry / Molecular Medicine / Pharmacology/Toxicology / Physiological aspects / review-article / Vehicles