TY - JOUR
T1 - PAMAM dendrimers cross the blood–brain barrier when administered through the carotid artery in C57BL/6J mice
AU - Srinageshwar, Bhairavi
AU - Peruzzaro, Sarah
AU - Andrews, Melissa
AU - Johnson, Kayla
AU - Hietpas, Allison
AU - Clark, Brittany
AU - McGuire, Crystal
AU - Petersen, Eric
AU - Kippe, Jordyn
AU - Stewart, Andrew
AU - Lossia, Olivia
AU - Al-Gharaibeh, Abeer
AU - Antcliff, Aaron
AU - Culver, Rebecca
AU - Swanson, Douglas
AU - Dunbar, Gary
AU - Sharma, Ajit
AU - Rossignol, Julien
N1 - Funding Information:
We would like to thank Michael Sandstrom at Central Michigan University for generously contributing the materials required for making the catheters for the carotid injection. Support for this study was provided by the Program in Neuroscience, the College of Medicine, the Chemistry & Biochemistry Department, and the John G. Kulhavi Professorship in Neuroscience at Central Michigan University and the Field Neurosciences Institute.
Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2017/3/14
Y1 - 2017/3/14
N2 - 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.
AB - 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.
KW - Bio-distribution and uptake
KW - Blood–brain barrier
KW - Neurodegenerative diseases
KW - Non-invasive delivery
KW - PAMAM dendrimer nanoparticle
UR - http://www.scopus.com/inward/record.url?scp=85015756577&partnerID=8YFLogxK
U2 - 10.3390/ijms18030628
DO - 10.3390/ijms18030628
M3 - Article
C2 - 28335421
AN - SCOPUS:85015756577
VL - 18
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 3
M1 - 628
ER -