Title:Recent Advances in Delivery Through the Blood-Brain Barrier
VOLUME: 14 ISSUE: 9
Author(s):Jessica M. Larsen, Douglas R. Martin and Mark E. Byrne
Affiliation:Biomimetic & Biohybrid Materials, Biomedical Devices, and Drug Delivery Laboratories, Department of Chemical Engineering, Samuel Ginn College of Engineering, Auburn, AL 36849, U.S.A.
Keywords:Blood-brain barrier, carrier mediated delivery, controlled drug delivery, intravenous delivery, nanocarriers,
nanoparticulate carriers.
Abstract:Current routes of delivering therapeutics to the brain to treat a variety of neurologic conditions include intracerebral,
intrathecal, and intranasal delivery. Though successes have been achieved through the use of these methods, each
has limitations that warrant a more universal delivery system involving the intravenous pathway. Two main barriers to intravenous
delivery are the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier. This review discusses potential
methods for overcoming barriers of intravenous-mediated brain targeting as well as highlights aspects of the highly
restrictive BBB anatomy that are important to consider in the design of successful drug delivery systems. Recent advances
in intravenous delivery to the brain have exploited receptor-mediated transcytosis and BBB disruption, as well as control
of carrier properties. Currently, three predominant synthetic carriers are being studied to transport therapeutics across the
BBB: liposomes, metallic nanoparticles, and polymersomes. This article also focuses on receptors that may be upregulated
by brain endothelial cells and their ability to significantly increase brain tissue drug distribution when specific
targeting moieties to these receptors are attached to synthetic nanocarriers.