Endocytosis at the blood-brain barrier: from basic understanding to drug delivery strategies.
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.
Smith
Mathew W
MW
Pharmaceutical Cell Biology, Welsh School of Pharmacy, Cardiff University, Redwood Building, Cardiff CF10 3XF, UK.
Gumbleton
Mark
M
D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000502:physiology*; D002417:Cattle; D002491:Central Nervous System Agents / Q000008:administration & dosage*; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004705:Endocytosis; D006801:Humans; D051379:Mice; D051381:Rats
D002491:Central Nervous System Agents; D004337:Drug Carriers