Surface-Modified G4 PAMAM Dendrimers Cross the Blood-Brain Barrier Following Multiple Tail-Vein Injections in C57BL/6J Mice.
PAMAM dendrimer
blood-brain barrier
multiple injections
systemic injections, dendrimer surface
tail-vein injections
Journal
ACS chemical neuroscience
ISSN: 1948-7193
Titre abrégé: ACS Chem Neurosci
Pays: United States
ID NLM: 101525337
Informations de publication
Date de publication:
18 09 2019
18 09 2019
Historique:
pubmed:
8
8
2019
medline:
12
9
2020
entrez:
8
8
2019
Statut:
ppublish
Résumé
Intracranial injections are currently used to deliver drugs into the brain, as most drugs cannot cross the blood-brain barrier (BBB) following systemic injections. Moreover, multiple dosing is difficult with invasive techniques. Therefore, viable systemic techniques are necessary to facilitate treatment paradigms that require multiple dosing of therapeutics across the BBB. In this study, we show that mixed-surface fourth-generation poly(amidoamine) (PAMAM) dendrimers containing predominantly biocompatible hydroxyl groups and a few amine groups are taken up by cultured primary cortical neurons derived from mouse embryo. We also show that these dendrimers cross the BBB following their administration to healthy mice in multiple doses via tail-vein injections and are taken up by neurons and the glial cells as evidenced by appropriate staining methods. Besides the brain, the dendrimers were found mostly in the kidneys compared to other peripheral organs, such as liver, lungs, and spleen, implying that they may be readily excreted, thereby preventing potential toxic accumulation in the body. Our findings provide a proof-of-concept that appropriate surface modifications of dendrimers provide safe, biocompatible nanomaterial with the potential to deliver therapeutic cargo across the BBB into the brain via multiple tail-vein injections.
Identifiants
pubmed: 31390175
doi: 10.1021/acschemneuro.9b00347
pmc: PMC9271804
mid: NIHMS1821748
doi:
Substances chimiques
Dendrimers
0
Nylons
0
PAMAM-G4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4145-4150Subventions
Organisme : NEI NIH HHS
ID : R21 EY030012
Pays : United States
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