Surface-Modified G4 PAMAM Dendrimers Cross the Blood-Brain Barrier following Multiple Tail-Vein Injections in C57BL/6J Mice

Bhairavi Srinageshwar, Anthony Dils, John Sturgis, Anna Wedster, Balachandar Kathirvelu, Stephanie Baiyasi, Douglas Swanson, Ajit Sharma, Gary L. Dunbar, Julien Rossignol

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)4145-4150
Number of pages6
JournalACS Chemical Neuroscience
Volume10
Issue number9
DOIs
StatePublished - Sep 18 2019

Keywords

  • PAMAM dendrimer
  • blood-brain barrier
  • dendrimer surface
  • multiple injections
  • systemic injections
  • tail-vein injections

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