Targeting receptor-ligand chemistry for drug delivery across blood-brain barrier in brain diseases

Anthony, Danielle Paige and Hegde, Manasa and Shetty, Shreya S and Rafic, Thasneema and Mutalik, Srinivas and Rao, Satish BS (2021) Targeting receptor-ligand chemistry for drug delivery across blood-brain barrier in brain diseases. Life Sciences, 274. pp. 1-15. ISSN 0024-3205

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Abstract

The blood-brain barrier (BBB) is composed of a layer of endothelial cells that is interspersed with a series of tight junctions and characterized by the absence of fenestrations. The permeability of this barrier is controlled by junctions such as tight junctions and adherent junctions as well as several cells such as astrocytes, pericytes, vascular endothelial cells, neurons, microglia, and efflux transporters with relatively enhanced expression. It plays a major role in maintaining homeostasis in the brain and exerts a protective regulatory control on the influx and efflux of molecules. However, it proves to be a challenge for drug delivery strategies that target brain diseases like Dementia, Parkinson’s Disease, Alzheimer’s Disease, Brain Cancer or Stroke, Huntington’s Disease, Lou Gehrig’s Disease, etc. Conventional modes of drug delivery are invasive and have been known to contribute to a “leaky BBB”, recent studies have highlighted the efficiency and relative safety of receptor-mediated drug delivery. Several receptors are exhibited on the BBB, and actively participate in nutrient uptake, and recognize specific ligands that modulate the process of endocytosis. The strategy employed in receptor-mediated drug delivery exploits this process of “tricking” the receptors into internalizing ligands that are conjugated to carrier systems like liposomes, nanoparticles, monoclonal antibodies, enzymes etc. These in turn are modified with drug molecules, therefore leading to delivery to desired target cells in brain tissue. This review comprehensively explores each of those receptors that can be modified to serve such purposes as well as the currently employed strategies that have led to increased cellular uptake and transport efficiency.

Item Type: Article
Uncontrolled Keywords: Blood-brain barrier; nanoparticles; receptor mediated-drug delivery.
Subjects: Life Sciences > MLSC Manipal
Depositing User: KMC Library
Date Deposited: 29 Mar 2022 11:36
Last Modified: 29 Mar 2022 11:36
URI: http://eprints.manipal.edu/id/eprint/158504

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