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

doi:10.1016/j.nano.2016.01.002

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

Nanomedicine. 2016 Jul;12(5):1219-29. doi: 10.1016/j.nano.2016.01.002. Epub 2016 Mar 3.

Authors

Il-Doo Kim¹, Elizabeth Sawicki², Hye-Kyung Lee¹, Eun-Hwa Lee³, Heon Joo Park⁴, Pyung-Lim Han³, Kyekyoon Kevin Kim⁵, Hyungsoo Choi⁶, Ja-Kyeong Lee⁷

Affiliations

¹ Department of Anatomy, Inha University School of Medicine, Inchon, Korea; Medical Research Center, Inha University School of Medicine, Inchon, Korea.
² Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
³ Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, Republic of Korea.
⁴ Medical Research Center, Inha University School of Medicine, Inchon, Korea; Department of Microbiology, Inha University School of Medicine, Inchon, Korea.
⁵ Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL USA.
⁶ Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL USA.
⁷ Department of Anatomy, Inha University School of Medicine, Inchon, Korea; Medical Research Center, Inha University School of Medicine, Inchon, Korea. Electronic address: jklee@inha.ac.kr.

PMID: 26945975
DOI: 10.1016/j.nano.2016.01.002

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.

Keywords: Gelatin nanoparticles; Intranasal delivery; MCAO; iNOS; siRNA.

MeSH terms

Administration, Intranasal
Animals
Brain
Gelatin
Infarction, Middle Cerebral Artery / drug therapy
Nanoparticles*
Neuroprotective Agents / administration & dosage*
RNA, Small Interfering / administration & dosage*
Rats

Substances

Neuroprotective Agents
RNA, Small Interfering
Gelatin