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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. Shusta
Research Paper

Abstract

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 

Abbreviations

ADR

adriamycin

AEM

analytical electron microscopy

AUC

area under the curve

Av

avidin

AZT

azidothymidine

BBB

blood–brain barrier

BDNF

brain-derived neurotrophic factor

bFGF

basic fibroblast growth factor

DSPE

distearoylphosphatidylethanolamine

EGFR

human epidermal growth factor receptor

FGF-2

fibroblast growth factor-2

GFAP

glial fibrillary acidic protein

GUS

β-glucuronidase

HB-EGF

heparin binding epidermal growth factor-like growth factor

HCEC

human cerebromicrovascular endothelial cells

HD

Huntington’s disease

HIR

human insulin receptor

HRP

horseradish peroxidase

IGF-II

insulin-like growth factor II

LDL

low density lipoprotein

LRP1/2

low density lipoprotein receptor-related protein 1/2

M6P

mannose 6-phosphate

MAb

monoclonal antibody

MCAO

middle cerebral artery occlusion

NGF

nerve growth factor

NHS

N-hydroxysuccinimide

ODN

oligonucleotides

PBCA

poly(butyl cyanoacrylate)

PEG

poly(ethylene glycol)

P-GUS

phosphorylated β-glucuronidase

PNA

peptide nucleic acid

RAP

receptor-associated protein

RES

reticuloendothelial system

RMT

receptor-mediated transcytosis

rsCD4

recombinant human soluble CD4

SA/B

streptavidin/ biotin

SATA

N-succinimidyl S-acetylthioacetate

scFv

single-chain variable fragment

sdAb

single-domain antibodies

SMCC

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

SV40

simian virus 40

Tf

transferrin

TfR

transferrin receptor

TH

tyrosine hydroxylase

tPA

tissue-type plasminogen activator

VIP

vasoactive intestinal peptide

Notes

Acknowledgments

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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