Intrinsic targeting of inflammatory cells in the brain by polyamidoamine dendrimers upon subarachnoid administration

Hui Dai, Raghavendra S. Navath, Bindu Balakrishnan, Bharath Raja Guru, Manoj K. Mishra, Roberto Romero, Rangaramanujam M. Kannan, Sujatha Kannan

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Aim: Understanding the interactions between nanomaterials and disease processes is crucial for designing effective therapeutic approaches. This article explores the unusual neuroinflammation targeting of dendrimers (with no targeting ligands) in the brain, with significant consequences for nanoscale materials in medicine. Method: The in vivo biodistribution of fluorescent-labeled neutral generation-4- polyamidoamine dendrimers (∼4 nm) in a rabbit model of cerebral palsy was explored following subarachnoid administration. Results: These dendrimers, with no targeting ligands, were localizing in activated microglia and astrocytes (cells responsible for neuroinflammation), even in regions far moved from the site of injection, in newborn rabbits with maternal inflammation-induced cerebral palsy. Conclusion: This intrinsic ability of dendrimers to localize inactivated microglia and astrocytes can enable targeted delivery of therapeutics in disorders such as cerebral palsy, Alzheimer's and multiple sclerosis.

Original languageEnglish (US)
Pages (from-to)1317-1329
Number of pages13
JournalNanomedicine
Volume5
Issue number9
DOIs
StatePublished - Nov 2010
Externally publishedYes

Keywords

  • PAMAM dendrimers
  • cerebral palsy
  • microglia-targeted drug delivery to the brain
  • neuroinflammation

ASJC Scopus subject areas

  • Bioengineering
  • Development
  • Biomedical Engineering
  • General Materials Science
  • Medicine (miscellaneous)

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