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Targeting Receptor-Mediated Transport for Delivery of Biologics Across the Blood-Brain Barrier
Open accessAbstract
Biologics are an emerging class of medicines with substantial promise to treat neurological disorders such as Alzheimer's disease, stroke, and multiple sclerosis. However, the blood-brain barrier (BBB) presents a formidable obstacle that appreciably limits brain uptake and hence the therapeutic potential of biologics following intravenous administration. One promising strategy for overcoming the BBB to deliver biologics is the targeting of endogenous receptor-mediated transport (RMT) systems that employ vesicular trafficking to transport ligands across the BBB endothelium. If a biologic is modified with an appropriate targeting ligand, it can gain improved access to the brain via RMT. Various RMT-targeting strategies have been developed over the past 20 years, and this review explores exciting recent advances, emphasizing studies that show brain targeting in vivo.
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“Nanoparticle-based drug delivery systems aim to overcome these challenges by exploiting specialized BBB transport mechanisms, primarily receptor-mediated transcytosis (RMT) and adsorptive-mediated transcytosis (AMT) [8, 9].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [8]
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“AMT is based on electrostatic interactions between positively charged NPs and the negatively charged luminal surface of endothelial cell membranes, primarily due to the presence of heparan sulfate proteoglycans and other anionic residues [8].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [8]
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Metadata
- Authors
- Lajoie, J. M., & Shusta, E. V.
- Affiliations
- University of Wisconsin–Madison (US)
- ORCID
- Shusta, Eric V.
- Venue
- Annual Review of Pharmacology and Toxicology
- Publisher
- Annual Reviews
- Published
- 2015-01-06
- Volume
- 55
- Issue
- 1
- Pages
- 613-631
- ISSN
- 0362-1642 (ISSN-L)
- 1545-4304
- PMC
- PMC5051266
- OpenAlex
- W2169055592
- Cited by
- 399
- References
- 124
- Citations by year
- 2026: 23 · 2025: 35 · 2024: 43 · 2023: 41 · 2022: 52 · 2021: 49 · 2020: 42 · 2019: 30 · 2018: 36 · 2017: 22 · 2016: 21 · 2015: 5
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Annual Review of Pharmacology and Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Human Genome Research Institute (T32HG002760)
- National Institute of General Medical Sciences (T32GM008349)
- National Institute of Neurological Disorders and Stroke (R01NS071513)
- 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 transport, biologics, BBB crossing, vesicle trafficking, targeting ligands, neurological disorders, Alzheimer's disease, stroke, multiple sclerosis
- MeSH terms
- Animals, Biological Products, Biological Transport, Blood-Brain Barrier, Capillary Permeability, Chemistry, Pharmaceutical, Drug Carriers, Humans, Receptors, Cell Surface, Technology, Pharmaceutical
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