Tight junction modulation of the blood brain barrier: CNS delivery of small molecules

• Published in: Tissue barriers Vol. 4; no. 1; p. e1138017
• Main Authors: Greene, Chris, Campbell, Matthew
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 02.01.2016
• Subjects: Animals; Blood-Brain Barrier - cytology; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Capillary Permeability; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Humans; Review; Tight Junction Proteins - metabolism; Tight Junctions - drug effects; Tight Junctions - metabolism
• ISSN: 2168-8370; 2168-8362; 2168-8370
• DOI: 10.1080/21688370.2015.1138017

The blood brain barrier (BBB) represents a major obstacle for targeted drug delivery to the brain for the treatment of central nervous system (CNS) disorders. Significant advances in barrier research over the past decade has led to the discovery of an increasing number of structural and regulatory proteins in tight junctions (TJ) and adherens junctions (AJ). These discoveries are providing the framework for the development of novel TJ modulators which can act specifically and temporarily to alter BBB function and regulate paracellular uptake of molecules. TJ modulators that have shown therapeutic potential in preclinical models include claudin-5 and occludin siRNAs, peptides derived from zonula occludens toxin as well as synthetic peptides targeting the extracellular loops of TJs. Adding to the array of modulating agents are novel mechanisms of BBB regulation such as focused ultrasound (FUS). This review will give a succinct overview of BBB biology and TJ modulation in general. Novel insights into BBB regulation in health and disease will also be summarized.