Robust neuroprotective effects of intranasally delivered iNOS siRNA encapsulated in gelatin nanoparticles in the postischemic brain

Il Doo Kim, Elizabeth Sawicki, Hye Kyung Lee, Eun Hwa Lee, Heon Joo Park, Pyung Lim Han, Kyekyoon Kevin Kim, Hyungsoo Choi, Ja Kyeong Lee

Research output: Contribution to journalArticlepeer-review

Abstract

The therapeutic efficacy of intranasal iNOS siRNA delivery was investigated in the postischemic rat brain after encapsulating on in gelatin nanoparticles (GNPs; diameter 188.0 ± 60.9 nm) cross-linked with 0.0667% glutaraldehyde (GA). Intranasally delivered GNPs were found in extracellular and intracellular compartments of many brain regions, including the olfactory bulb, cerebral cortex, and striatum at 1 hour after infusion and continued to be detected for days. Infarct volumes were markedly suppressed (maximal reduction to 42.1 ± 2.6%) at 2 days after 60 minutes of middle cerebral artery occlusion (MCAO) when iNOS siRNA/GNPs were delivered at 6 hours post-MCAO. In addition, this protective effect was manifested by reductions in neurological and behavioral deficits that were sustained for 2 weeks. Therapeutic potency of iNOS siRNA/GNPs was significantly greater and sustained longer than that of bare siRNA and prolonged and efficient iNOS by iNOS siRNA/GNP is responsible for the robust neuroprotective effect.

Original languageEnglish (US)
Pages (from-to)1219-1229
Number of pages11
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume12
Issue number5
DOIs
StatePublished - Jul 1 2016

Keywords

  • Gelatin nanoparticles
  • INOS
  • Intranasal delivery
  • MCAO
  • SiRNA

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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