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

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

Divison of Brain & Cognitive Sciences

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

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 language	English
Pages (from-to)	1219-1229
Number of pages	11
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	12
Issue number	5
DOIs	https://doi.org/10.1016/j.nano.2016.01.002
State	Published - 1 Jul 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc.

Keywords

Gelatin nanoparticles
INOS
Intranasal delivery
MCAO
SiRNA

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10.1016/j.nano.2016.01.002

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title = "Robust neuroprotective effects of intranasally delivered iNOS siRNA encapsulated in gelatin nanoparticles in the postischemic brain",

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, INOS, Intranasal delivery, MCAO, SiRNA",

author = "Kim, \{Il Doo\} and Elizabeth Sawicki and Lee, \{Hye Kyung\} and Lee, \{Eun Hwa\} and Park, \{Heon Joo\} and Han, \{Pyung Lim\} and Kim, \{Kyekyoon Kevin\} and Hyungsoo Choi and Lee, \{Ja Kyeong\}",

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doi = "10.1016/j.nano.2016.01.002",

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AU - Kim, Il Doo

AU - Sawicki, Elizabeth

AU - Lee, Hye Kyung

AU - Lee, Eun Hwa

AU - Park, Heon Joo

AU - Han, Pyung Lim

AU - Kim, Kyekyoon Kevin

AU - Choi, Hyungsoo

AU - Lee, Ja Kyeong

PY - 2016/7/1

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N2 - 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.

AB - 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.

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KW - Intranasal delivery

KW - MCAO

KW - SiRNA

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ER -

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

Abstract

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Keywords

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