Frontiers in Neuroanatomy (Mar 2014)

Distribution of nanoparticles throughout the cerebral cortex of rodents and non-human primates: Implications for gene and drug therapy

  • Ernesto A Salegio,
  • Ernesto A Salegio,
  • Hillary eStreeter,
  • Nikhil eDube,
  • Piotr eHadaczek,
  • Lluis eSamaranch,
  • Adrian eKells,
  • Waldy eSan Sebastián,
  • Yuying eZhai,
  • John eBringas,
  • Ting eXu,
  • John eForsayeth,
  • Krystof S Bankiewicz

DOI
https://doi.org/10.3389/fnana.2014.00009
Journal volume & issue
Vol. 8

Abstract

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When nanoparticles/proteins are infused into the brain, they are often transported to distal sites in a manner that is dependent both on the characteristics of the infusate and the region targeted. We have previously shown that AAV is disseminated within the brain by perivascular flow and also by axonal transport. Perivascular distribution usually does not depend strongly on the nature of the infusate. Many proteins, neutral liposomes and AAV particles distribute equally well by this route when infused under pressure into various parenchymal locations. In contrast, axonal transport requires receptor-mediated uptake of AAV by neurons and engagement with specific transport mechanisms previously demonstrated for other neurotropic viruses. Cerebrospinal fluid represents yet another way in which brain anatomy may be exploited to distribute nanoparticles broadly in the central nervous system. In this study, we assessed the distribution and perivascular transport of nanoparticles of different sizes delivered into the parenchyma of rodents and cerebrospinal fluid in non-human primates.

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