Development of Novel Therapeutics Targeting the Blood–Brain Barrier: From Barrier to Carrier

• Published in: Advanced science Vol. 8; no. 16; pp. e2101090 - n/a
• Main Authors: Li, Jia, Zheng, Meng, Shimoni, Olga, Banks, William A., Bush, Ashley I., Gamble, Jennifer R., Shi, Bingyang
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.08.2021; John Wiley and Sons Inc; Wiley
• Subjects: Alzheimer's disease; Animals; Biological Transport; Blood-Brain Barrier - metabolism; blood–brain barrier; brain diseases; DNA methylation; Drug Carriers - administration & dosage; drug delivery; Drug Delivery Systems; Drugs; Endothelium; Gene expression; Humans; Inflammation; Mice; nanomedicine; Nanoparticle Drug Delivery System - administration & dosage; nanotechnology; Proteins; Review; Reviews; Veins & arteries; blood-brain barrier; nanotechnology; nanomedicine; drug delivery; brain diseases
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202101090

The blood–brain barrier (BBB) is a highly specialized neurovascular unit, initially described as an intact barrier to prevent toxins, pathogens, and potentially harmful substances from entering the brain. An intact BBB is also critical for the maintenance of normal neuronal function. In cerebral vascular diseases and neurological disorders, the BBB can be disrupted, contributing to disease progression. While restoration of BBB integrity serves as a robust biomarker of better clinical outcomes, the restrictive nature of the intact BBB presents a major hurdle for delivery of therapeutics into the brain. Recent studies show that the BBB is actively engaged in crosstalk between neuronal and the circulatory systems, which defines another important role of the BBB: as an interfacing conduit that mediates communication between two sides of the BBB. This role has been subject to extensive investigation for brain‐targeted drug delivery and shows promising results. The dual roles of the BBB make it a unique target for drug development. Here, recent developments and novel strategies to target the BBB for therapeutic purposes are reviewed, from both barrier and carrier perspectives. Blood–brain barrier (BBB), which separates the blood and the brain, plays a critical protective role in brain homeostasis. However, it is also a formidable barrier for brain‐targeted drug delivery. This review summarizes the key strategies to restore BBB integrity and to penetrate the BBB for drug delivery, in particular, under neuroinflammation conditions.