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

Publication date: Available online 3 March 2016 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): 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 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 hr 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 min of middle cerebral artery occlusion (MCAO) when iNOS siRNA/GNPs were delivered at 6 hrs post-MCAO. In addition, this protective effect was manifested by reductions in neurological and behavioral deficits that were sustained for two weeks. Therapeutic potency of iNOS siRNA/GNPs was significantly greater and sustained longer than that of bare siRNA and prolonged and efficient iNOS of iNOS by iNOS siRNA/GNP is responsible for the robust neuroprotective effect. Graphical abstract
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research