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Pharmaceutics 2014, 6(4), 557-583; doi:10.3390/pharmaceutics6040557

Smuggling Drugs into the Brain: An Overview of Ligands Targeting Transcytosis for Drug Delivery across the Blood–Brain Barrier

Department of Cell Biology, University Medical Center Groningen, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands
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Received: 24 September 2014 / Revised: 28 October 2014 / Accepted: 29 October 2014 / Published: 17 November 2014
(This article belongs to the Special Issue Drug Delivery to Brain)
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Abstract

The blood–brain barrier acts as a physical barrier that prevents free entry of blood-derived substances, including those intended for therapeutic applications. The development of molecular Trojan horses is a promising drug targeting technology that allows for non-invasive delivery of therapeutics into the brain. This concept relies on the application of natural or genetically engineered proteins or small peptides, capable of specifically ferrying a drug-payload that is either directly coupled or encapsulated in an appropriate nanocarrier, across the blood–brain barrier via receptor-mediated transcytosis. Specifically, in this process the nanocarrier–drug system (“Trojan horse complex”) is transported transcellularly across the brain endothelium, from the blood to the brain interface, essentially trailed by a native receptor. Naturally, only certain properties would favor a receptor to serve as a transporter for nanocarriers, coated with appropriate ligands. Here we briefly discuss brain microvascular endothelial receptors that have been explored until now, highlighting molecular features that govern the efficiency of nanocarrier-mediated drug delivery into the brain. View Full-Text
Keywords: blood–brain barrier; targeted drug delivery; nanocarriers; transcytosis blood–brain barrier; targeted drug delivery; nanocarriers; transcytosis
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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. (CC BY 4.0).

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Georgieva, J.V.; Hoekstra, D.; Zuhorn, I.S. Smuggling Drugs into the Brain: An Overview of Ligands Targeting Transcytosis for Drug Delivery across the Blood–Brain Barrier. Pharmaceutics 2014, 6, 557-583.

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