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International Journal of Cell Biology
Volume 2013 (2013), Article ID 703545, 14 pages
Review Article

Receptor-Mediated Endocytosis and Brain Delivery of Therapeutic Biologics

Drug Metabolism and Pharmacokinetics, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA

Received 23 January 2013; Accepted 13 May 2013

Academic Editor: Afshin Samali

Copyright © 2013 Guangqing Xiao and Liang-Shang Gan. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Transport of macromolecules across the blood-brain-barrier (BBB) requires both specific and nonspecific interactions between macromolecules and proteins/receptors expressed on the luminal and/or the abluminal surfaces of the brain capillary endothelial cells. Endocytosis and transcytosis play important roles in the distribution of macromolecules. Due to the tight junction of BBB, brain delivery of traditional therapeutic proteins with large molecular weight is generally not possible. There are multiple pathways through which macromolecules can be taken up into cells through both specific and nonspecific interactions with proteins/receptors on the cell surface. This review is focused on the current knowledge of receptor-mediated endocytosis/transcytosis and brain delivery using the Angiopep-2-conjugated system and the molecular Trojan horses. In addition, the role of neonatal Fc receptor (FcRn) in regulating the efflux of Immunoglobulin G (IgG) from brain to blood, and approaches to improve the pharmacokinetics of therapeutic biologics by generating Fc fusion proteins, and increasing the pH dependent binding affinity between Fc and FcRn, are discussed.