Strategies for delivering therapeutics across the blood–brain barrier
Abstract
Achieving sufficient delivery across the blood-brain barrier is a key challenge in the development of drugs to treat central nervous system (CNS) disorders. This is particularly the case for biopharmaceuticals such as monoclonal antibodies and enzyme replacement therapies, which are largely excluded from the brain following systemic administration. In recent years, increasing research efforts by pharmaceutical and biotechnology companies, academic institutions and public-private consortia have resulted in the evaluation of various technologies developed to deliver therapeutics to the CNS, some of which have entered clinical testing. Here we review recent developments and challenges related to selected blood-brain barrier-crossing strategies - with a focus on non-invasive approaches such as receptor-mediated transcytosis and the use of neurotropic viruses, nanoparticles and exosomes - and analyse their potential in the treatment of CNS disorders.
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Several approaches can mediate crossing of the blood-brain barrier, including passive diffusion and adsorptive-mediated, carrier-mediated and receptor-mediated transcytosis.
“Previous studies have reported that several approaches can mediate the crossing of the BBB, including passive diffusion and adsorptive-mediated, carrier-mediated and receptor-mediated transcytosis25.”
From Blood–brain-barrier-crossing lipid nanoparticles for mRNA delivery to the central nervous system (2025) · cites this paper as [25]
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- Authors
- Terstappen, G. C., Meyer, A. H., Bell, R. D., & Zhang, W.
- Affiliations
- AbbVie (Germany) (DE)
- Pfizer (United States) (US)
- University of Ottawa (CA)
- Corresponding author
- Terstappen, Georg C.
- Venue
- Nature Reviews Drug Discovery
- Published
- 2021-03-01
- Volume
- 20
- Issue
- 5
- Pages
- 362-383
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W3134309694
- Cited by
- 1,138
- References
- 31
- Citations by year
- 2026: 186 · 2025: 317 · 2024: 249 · 2023: 231 · 2022: 125 · 2021: 29
- FWCI
- 18.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- NPARC (submittedVersion)
- 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, brain drug delivery, receptor-mediated transcytosis, neurotropic viruses, nanoparticles, exosomes, monoclonal antibodies, enzyme replacement therapy, central nervous system disorders
- MeSH terms
- Animals, Blood-Brain Barrier, Central Nervous System Agents, Central Nervous System Diseases, Humans, Drug Delivery Systems
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