Mechanism of polymeric nanoparticle-based drug transport across the blood-brain barrier (bbb).
Abstract
In 1995 it was reported for the first time that nanoparticles could be used for the delivery of drugs across the blood-brain barrier (BBB) following intravenous injection. In vitro and in vivo experiments show that the underlying mechanism is receptor-mediated endocytosis followed by transcytosis. No opening of the tight junctions was observed. Due to the overcoating of the nanoparticles with polysorbate 80 or poloxamers 188, apolipoproteins A-I and/or E are adsorbed from the blood on to the particle surface after injection. These apolipoproteins mediate the interaction with LDL or scavenger receptors on the BBB followed by the above brain uptake processes. Likewise, covalent attachment of these apolipoproteins or of transferrin, insulin or antibodies against the respective receptors also enables a similar nanoparticle-mediated drug transport across the BBB. From these results it can be concluded that the nanoparticles act as "Trojan Horses" taking advantage of physiological receptor-mediated transport processes across the BBB.
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A possible mechanism of PS80-coated PACA nanoparticle delivery is adsorption on ApoE and B from the bloodstream upon intravenous injection followed by transcytosis across the BBB using low-density lipoprotein receptors.
“A possible mechanism of such delivery is adsorption of PS80-coated PACA nanoparticles on ApoE and B from the bloodstream upon intravenous injection followed by transcytosis across BBB using the low-density lipoprotein receptors (Kreuter, 2013).”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Kreuter, 2013
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- Authors
- Kreuter, J.
- Affiliations
- Goethe University Frankfurt (DE)
- Corresponding author
- Kreuter, Jörg
- Venue
- Journal of Microencapsulation
- Publisher
- Informa UK Limited
- Published
- 2012-06-07
- Volume
- 30
- Issue
- 1
- Pages
- 49-54
- ISSN
- 0265-2048 (ISSN-L)
- 1464-5246
- OpenAlex
- W2139835982
- Cited by
- 172
- References
- 50
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 10 · 2023: 14 · 2022: 11 · 2021: 11 · 2020: 20 · 2019: 13 · 2018: 10 · 2017: 10 · 2016: 23 · 2015: 20 · 2014: 7 · 2013: 7 · 2012: 2
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Microencapsulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- blood-brain barrier, polymeric nanoparticles, nanoparticle drug delivery, receptor-mediated endocytosis, transcytosis, tight junctions, apolipoprotein A-I, apolipoprotein E, LDL receptor, scavenger receptors, transferrin, insulin, poloxamer 188, Tween 80, Trojan horse
- MeSH terms
- Animals, Blood-Brain Barrier, Doxorubicin, Polymers, Nerve Growth Factor, Mice, Nanoparticles
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