Endocytosis at the blood-brain barrier: From basic understanding to drug delivery strategies

Smith, Mathew W. ORCID: https://orcid.org/0000-0002-5697-0204 and Gumbleton, Mark ORCID: https://orcid.org/0000-0002-7386-311X 2006. Endocytosis at the blood-brain barrier: From basic understanding to drug delivery strategies. Journal of Drug Targeting 14 (4) , pp. 191-214. 10.1080/10611860600650086

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Abstract

The blood–brain barrier (BBB) protects the central nervous system (CNS) from potentially harmful xenobiotics and endogenous molecules. Anatomically, it comprises the brain microvasculature whose functionality is nevertheless influenced by associated astrocyte, pericyte and neuronal cells. The highly restrictive paracellular pathway within brain microvasculature restricts significant CNS penetration to only those drugs whose physicochemical properties afford ready penetration into hydrophobic cell membranes or are capable of exploiting endogenous active transport processes such as solute carriers or endocytosis pathways. Endocytosis at the BBB is an essential pathway by which the brain obtains its nutrients and affords communication with the periphery. The development of strategies to exploit these endocytic pathways for the purposes of drug delivery to the CNS is still an immature field although some impressive results have been documented with the targeting of particular receptors. This current article initially provides an overview of general endocytosis processes and pathways showing evidence of their functional existence within the BBB. Subsequent sections provide, in an entity-specific manner, comprehensive reviews on BBB transport investigations of endocytosis involving: transferrin and the targeting of the transferrin receptor; hormones; cytokines; cell penetrating peptides; microorganisms and toxins, and nanoparticles aimed at more effectively delivering drugs to the CNS.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Blood–brain barrier, endocytosis and transcytosis, transferrin, leptin, ghrelin, insulin
Publisher:	Taylor & Francis
ISSN:	1061-186X
Last Modified:	27 Oct 2022 10:03
URI:	https://orca.cardiff.ac.uk/id/eprint/68794

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