Cited by 110Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsNanoparticle-Based Drug Delivery

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

Anthony, Danielle Paige, Hegde, Manasa, Shetty, Shreya S., Rafic, Thasneema, Mutalik, Srinivas, Rao, B.S. Satish·2021·Life Sciences

DOI 10.1016/j.lfs.2021.119326

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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.

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Authors: Anthony, D. P., Hegde, M., Shetty, S. S., Rafic, T., Mutalik, S., & Rao, B. S. S.
Affiliations: Manipal Academy of Higher Education (IN)
Corresponding author: Rao, B.S. Satish
ORCID: Anthony, Danielle Paige
Rafic, Thasneema
Mutalik, Srinivas
Rao, B.S. Satish
Venue: Life Sciences
Publisher: Elsevier BV
Published: 2021-06
Volume: 274
Pages: 119326
ISSN: 0024-3205 (ISSN-L)
DOI: 10.1016/j.lfs.2021.119326
OpenAlex: W3135286150
Cited by: 110
References: 203
Citations by year: 2026: 10 · 2025: 30 · 2024: 31 · 2023: 16 · 2022: 18 · 2021: 5
FWCI: 2.05
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Life Sciences (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords: blood-brain barrier, receptor-mediated drug delivery, tight junctions, endocytosis, liposomes, nanoparticles, monoclonal antibodies, brain disorders, Alzheimer's disease, Parkinson's disease, brain cancer, stroke, Huntington's disease, efflux pumps
MeSH terms: Animals, Biological Transport, Blood-Brain Barrier, Brain Diseases, Central Nervous System Agents, Drug Carriers, Humans, Ligands, Permeability, Receptors, Cell Surface, Drug Delivery Systems

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

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