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
Department of Anatomy, Inha University School of Medicine, Inchon, Korea; Medical Research Center, Inha University School of Medicine, Inchon, Korea.
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Nanomedicine. 2016 Jul;12(5):1219-29. doi: 10.1016/j.nano.2016.01.002. Epub 2016 Mar 3.
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.
将诱导型一氧化氮合酶（iNOS）小干扰RNA（siRNA）包裹于用0.0667%戊二醛（GA）交联的明胶纳米颗粒（GNPs；直径188.0±60.9nm）中，研究其对大鼠脑缺血后经鼻给药的治疗效果。经鼻给药的GNPs在输注后1小时出现在包括嗅球、大脑皮层和纹状体在内的许多脑区的细胞外和细胞内区室中，并且在数天内持续被检测到。在大脑中动脉闭塞（MCAO）60分钟后6小时经鼻给予iNOS siRNA/GNPs，在MCAO后2天时梗死体积显著减小（最大减小至42.1±2.6%）。此外，这种保护作用表现为神经和行为缺陷的减轻，并持续2周。iNOS siRNA/GNPs的治疗效力明显高于裸siRNA，且持续时间更长，iNOS siRNA/GNP对iNOS的延长和有效抑制作用是产生强大神经保护作用的原因。
