Blood-brain barrier transport of therapeutics via receptor-mediation.
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.
Jones
Angela R
AR
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, Wisconsin 53706, USA.
Shusta
Eric V
EV
D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage; D001692:Biological Transport; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000502:physiology; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000502:physiology; D011972:Receptor, Insulin / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D011990:Receptors, Transferrin / Q000502:physiology
D001426:Bacterial Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; C028581:CRM197 (non-toxic variant of diphtheria toxin); D011972:Receptor, Insulin