Nanoscale effects in dendrimer-mediated targeting of neuroinflammation

Elizabeth Nance, Fan Zhang, Manoj K. Mishra, Zhi Zhang, Siva P. Kambhampati, Rangaramanujam M. Kannan, Sujatha Kannan

Research output: Contribution to journalArticlepeer-review

Abstract

Neuroinflammation, mediated by activated microglia and astrocytes, plays a key role in the pathogenesis of many neurological disorders. Systemically-administered dendrimers target neuroinflammation and deliver drugs with significant efficacy, without the need for ligands. Elucidating the nanoscale aspects of targeting neuroinflammation will enable superior nanodevices for eventual translation. Using a rabbit model of cerebral palsy, we studied the in vivo contributions of dendrimer physicochemical properties and disease pathophysiology on dendrimer brain uptake, diffusion, and cell specific localization. Neutral dendrimers move efficiently within the brain parenchyma and rapidly localize in glial cells in regions of injury. Dendrimer uptake is also dependent on the extent of blood-brain-barrier breakdown, glial activation, and disease severity (mild, moderate, or severe), which can lend the dendrimer to be used as an imaging biomarker for disease phenotype. This new understanding of the in vivo mechanism of dendrimer-mediated delivery in a clinically-relevant rabbit model provides greater opportunity for clinical translation of targeted brain injury therapies.

Original languageEnglish (US)
Pages (from-to)96-107
Number of pages12
JournalBiomaterials
Volume101
DOIs
StatePublished - Sep 1 2016

Keywords

  • Brain injury
  • Dendrimer
  • Glia
  • Nanoparticle
  • Neuroinflammation

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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