Pharmaceutical Research

, Volume 24, Issue 9, pp 1759–1771 | Cite as

Blood–Brain Barrier Transport of Therapeutics via Receptor-Mediation

  • Angela R. Jones
  • Eric V. ShustaEmail author
Research Paper


Drug delivery to the brain is hindered by the presence of the blood–brain barrier (BBB). Although the BBB restricts the passage of many substances, it is actually selectively permeable to nutrients necessary for healthy brain function. To accomplish the task of nutrient transport, the brain endothelium is endowed with a diverse collection of molecular transport systems. One such class of transport system, known as a receptor-mediated transcytosis (RMT), employs the vesicular trafficking machinery of the endothelium to transport substrates between blood and brain. If appropriately targeted, RMT systems can also be used to shuttle a wide range of therapeutics into the brain in a noninvasive manner. Over the last decade, there have been significant developments in the arena of RMT-based brain drug transport, and this review will focus on those approaches that have been validated in an in vivo setting.

Key words

antibody blood–brain barrier brain drug delivery transcytosis 





analytical electron microscopy


area under the curve






blood–brain barrier


brain-derived neurotrophic factor


basic fibroblast growth factor




human epidermal growth factor receptor


fibroblast growth factor-2


glial fibrillary acidic protein




heparin binding epidermal growth factor-like growth factor


human cerebromicrovascular endothelial cells


Huntington’s disease


human insulin receptor


horseradish peroxidase


insulin-like growth factor II


low density lipoprotein


low density lipoprotein receptor-related protein 1/2


mannose 6-phosphate


monoclonal antibody


middle cerebral artery occlusion


nerve growth factor






poly(butyl cyanoacrylate)


poly(ethylene glycol)


phosphorylated β-glucuronidase


peptide nucleic acid


receptor-associated protein


reticuloendothelial system


receptor-mediated transcytosis


recombinant human soluble CD4


streptavidin/ biotin


N-succinimidyl S-acetylthioacetate


single-chain variable fragment


single-domain antibodies


Succinimidyl 4-[N-maleimidomethyl]-cyclohexane-1-carboxylate


simian virus 40




transferrin receptor


tyrosine hydroxylase


tissue-type plasminogen activator


vasoactive intestinal peptide



This work was in part funded by National Institutes of Health Grant NS052649. A.R.J. is the recipient of a National Science Foundation Graduate Research Fellowship.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Department of Chemical and Biological EngineeringUniversity of Wisconsin-MadisonMadisonUSA

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