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Int. J. Mol. Sci. 2017, 18(3), 628; doi:10.3390/ijms18030628

PAMAM Dendrimers Cross the Blood–Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice

1
Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA
2
Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA
3
Department of Chemistry & Biochemistry Central Michigan University, Mount Pleasant, MI 48859, USA
4
Field Neurosciences Institute, St. Mary’s of Michigan, Saginaw, MI 48604, USA
5
College of Medicine, Central Michigan University, Mt. Pleasant, MI 48859, USA
6
Department of Psychology, Central Michigan University, Mt. Pleasant, MI 48859, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editors: Hari Shanker Sharma and Aruna Sharma
Received: 21 February 2017 / Revised: 10 March 2017 / Accepted: 10 March 2017 / Published: 14 March 2017
(This article belongs to the Special Issue Blood–Brain Barrier in CNS Injury and Repair)
View Full-Text   |   Download PDF [7056 KB, uploaded 14 March 2017]   |  

Abstract

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 View Full-Text
Keywords: PAMAM dendrimer nanoparticle; blood–brain barrier; non-invasive delivery; bio-distribution and uptake; neurodegenerative diseases PAMAM dendrimer nanoparticle; blood–brain barrier; non-invasive delivery; bio-distribution and uptake; neurodegenerative diseases
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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. PAMAM Dendrimers Cross the Blood–Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice. Int. J. Mol. Sci. 2017, 18, 628.

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