PAMAM Dendrimers Cross the Blood-Brain Barrier When Administered through the Carotid Artery in C57BL/6J Mice.
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.
Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA. srina1b@cmich.edu.|Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA. srina1b@cmich.edu.
Bhairavi
B
Srinageshwar
Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA. peruz1st@cmich.edu.|Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA. peruz1st@cmich.edu.
Sarah
S
Peruzzaro
Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA. andre2mm@cmich.edu.|Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA. andre2mm@cmich.edu.
Melissa
M
Andrews
Department of Chemistry & Biochemistry Central Michigan University, Mount Pleasant, MI 48859, USA. johns52k@cmich.edu.
Kayla
K
Johnson
Department of Chemistry & Biochemistry Central Michigan University, Mount Pleasant, MI 48859, USA. hietp1ar@cmich.edu.
Allison
A
Hietpas
Department of Chemistry & Biochemistry Central Michigan University, Mount Pleasant, MI 48859, USA. clark6bm@cmich.edu.
Brittany
B
Clark
Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA. mcgui4c@cmich.edu.|Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA. mcgui4c@cmich.edu.
Crystal
C
McGuire
Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA. peter1ed@cmich.edu.
Eric
E
Petersen
Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA. kippe1jm@cmich.edu.|Field Neurosciences Institute, St. Mary's of Michigan, Saginaw, MI 48604, USA. kippe1jm@cmich.edu.
Jordyn
J
Kippe
Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA. stewa2an@cmich.edu.|Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA. stewa2an@cmich.edu.
Andrew
A
Stewart
Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA. lossi1ov@cmich.edu.|Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA. lossi1ov@cmich.edu.|College of Medicine, Central Michigan University, Mt. Pleasant, MI 48859, USA. lossi1ov@cmich.edu.
Olivia
O
Lossia
Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA. algha2a@cmich.edu.|Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA. algha2a@cmich.edu.
Abeer
A
Al-Gharaibeh
Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA. antcl1ak@cmich.edu.|Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA. antcl1ak@cmich.edu.|College of Medicine, Central Michigan University, Mt. Pleasant, MI 48859, USA. antcl1ak@cmich.edu.
Aaron
A
Antcliff
Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA. culve1rl@cmich.edu.|Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA. culve1rl@cmich.edu.
Rebecca
R
Culver
Department of Chemistry & Biochemistry Central Michigan University, Mount Pleasant, MI 48859, USA. swans1d@cmich.edu.
Douglas
D
Swanson
Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA. dunba1g@cmich.edu.|Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA. dunba1g@cmich.edu.|Field Neurosciences Institute, St. Mary's of Michigan, Saginaw, MI 48604, USA. dunba1g@cmich.edu.|Department of Psychology, Central Michigan University, Mt. Pleasant, MI 48859, USA. dunba1g@cmich.edu.
Gary
G
Dunbar
Department of Chemistry & Biochemistry Central Michigan University, Mount Pleasant, MI 48859, USA. sharm1a@cmich.edu.
Ajit
A
Sharma
Field Neurosciences Institute laboratory for Restorative Neurology at Central Michigan University, Mt. Pleasant, MI 48859, USA. rossi1j@cmich.edu.|Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA. rossi1j@cmich.edu.|College of Medicine, Central Michigan University, Mt. Pleasant, MI 48859, USA. rossi1j@cmich.edu.
Julien
J
Rossignol
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002339:Carotid Arteries / Q000378:metabolism; D002478:Cells, Cultured; D050091:Dendrimers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D007269:Injections, Intra-Arterial; D051379:Mice; D008810:Mice, Inbred C57BL
D050091:Dendrimers; C104700:PAMAM Starburst
PAMAM dendrimer nanoparticle; bio-distribution and uptake; blood–brain barrier; neurodegenerative diseases; non-invasive delivery