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Robust neuroprotective effects of intranasally delivered iNOS siRNA encapsulated in gelatin nanoparticles in the postischemic brain
- Robust neuroprotective effects of intranasally delivered iNOS siRNA encapsulated in gelatin nanoparticles in the postischemic brain
- Kim, Il-Doo; Sawicki, Elizabeth; Lee, Hye-Kyung; Lee, Eun-Hwa; Park, Heon Joo; Han, Pyung-Lim; Kim, Kyekyoon (Kevin); Choi, Hyungsoo; Lee, Ja-Kyeong
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
- 1549-9634; 1549-9642
- vol. 12, no. 5, pp. 1219 - 1229
- Gelatin nanoparticles; iNOS; siRNA; MCAO; Intranasal delivery
- ELSEVIER SCIENCE BV
- SCIE; SCOPUS
- 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. (C) 2016 Elsevier Inc. All rights reserved.
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