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.
authors.affiliation: Department of Anatomy, Inha University School of Medicine, Inchon, Korea; Medical Research Center, Inha University School of Medicine, Inchon, Korea.
authors.forename: Il-Doo
authors.initials: ID
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sawicki
authors.affiliation: Department of Anatomy, Inha University School of Medicine, Inchon, Korea; Medical Research Center, Inha University School of Medicine, Inchon, Korea.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Eun-Hwa
authors.initials: EH
authors.lastname: Lee
authors.affiliation: Medical Research Center, Inha University School of Medicine, Inchon, Korea; Department of Microbiology, Inha University School of Medicine, Inchon, Korea.
authors.forename: Heon Joo
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Pyung-Lim
authors.initials: PL
authors.lastname: Han
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL USA.
authors.forename: Kyekyoon Kevin
authors.initials: KK
authors.lastname: Kim
authors.affiliation: Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL USA.
authors.forename: Hyungsoo
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Anatomy, Inha University School of Medicine, Inchon, Korea; Medical Research Center, Inha University School of Medicine, Inchon, Korea. Electronic address: jklee@inha.ac.kr.
authors.forename: Ja-Kyeong
authors.initials: JK
authors.lastname: Lee
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain; D005780:Gelatin; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy; D053758:Nanoparticles; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D051381:Rats
chemical_list: D018696:Neuroprotective Agents; D034741:RNA, Small Interfering; D005780:Gelatin
keywords: Gelatin nanoparticles; Intranasal delivery; MCAO; iNOS; siRNA