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

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• 作者：Il-Doo Kim ; PhD^a ; ^b ; Elizabeth Sawicki ; MD ; PhD^c ; Hye-Kyung Lee ; PhD^a ; ^b ; Eun-Hwa Lee ; PhD^d ; Heon Joo Park ; MD ; PhD^b ; ^e ; Pyung-Lim Han ; PhD^d ; Kyekyoon (Kevin) Kim ; PhD^c ; ^f ; Hyungsoo Choi ; PhD^f ; Ja-Kyeong Lee ; PhD^a ; ^b ; ^{jklee@inha.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Gelatin nanoparticles ; iNOS ; siRNA ; MCAO ; Intranasal delivery
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：12
• 期：5
• 页码：1219-1229
• 全文大小：1883 K

文摘

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.