PAMAM Dendrimers Cross the Blood–Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice
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Drug delivery into the central nervous system (CNS) is challenging due to the blood–brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the present study investigates the role of novel mixed surface dendrimers, which have potentially less toxicity and can cross the BBB when administered through the carotid artery in mice. In vitro experiments investigated the uptake of amine dendrimers (G1-NH2 and G4-NH2) and novel dendrimers (G1-90/10 and G4-90/10) by primary cortical cultures. In vivo experiments involved transplantation of G4-90/10 into mice through (1) invasive intracranial injections into the striatum; and (2) less invasive carotid injections. The animals were sacrificed 24-h and 1-week post-transplantations and their brains were analyzed. In vivo experiments proved that the G4-90/10 can cross the BBB when injected through the carotid artery and localize within neurons and glial cells. The dendrimers were found to migrate through the corpus callosum 1-week post intracranial injection. Immunohistochemistry showed that the migrating cells are the dendrimer-infected glial cells. Overall, our results suggest that poly-amidoamine (PAMAM) dendrimers may be used as a minimally invasive means to deliver biomolecules for treating neurological diseases or disorders
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Linking a drug to a poly-amidoamine dendrimer can overcome the blood-brain barrier.
“However, it can be achieved by linking the drug to a poly-amidoamine dendrimer to overcome the blood-brain barrier.31,32”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [31]
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Self-citation
- Authors
- Srinageshwar, B., Peruzzaro, S., Andrews, M., Johnson, K., Hietpas, A., Clark, B., McGuire, C., Petersen, E., Kippe, J., Stewart, A., Lossia, O., Al-Gharaibeh, A., Antcliff, A., Culver, R., Swanson, D., Dunbar, G., Sharma, A., & Rossignol, J.
- Affiliations
- Central Michigan University (US)
- Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA
- Corresponding author
- Rossignol, Julien
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2017-03-14
- Volume
- 18
- Issue
- 3
- Pages
- 628
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC5372641
- OpenAlex
- W2596420617
- Cited by
- 91
- References
- 27
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 8 · 2023: 12 · 2022: 9 · 2021: 10 · 2020: 10 · 2019: 12 · 2018: 11 · 2017: 1
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Central Michigan University
- Field Neurosciences Institute
- Topics
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- PAMAM dendrimers, blood-brain barrier penetration, carotid artery injection, intracranial injection, corpus callosum, brain drug delivery, dendrimer toxicity
- MeSH terms
- Animals, Blood-Brain Barrier, Carotid Arteries, Cells, Cultured, Injections, Intra-Arterial, Mice, Inbred C57BL, Dendrimers, Mice
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