Intranasal Brain Delivery of Cationic Nanoemulsion-Encapsulated TNFα siRNA in Prevention of Experimental Neuroinflammation

Publication date: Available online 6 January 2016 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Sunita Yadav, Srujan K. Gandham, Riccardo Panicucci, Mansoor M. Amiji Neuroinflammation is a hallmark of acute and chronic neurodegenerative disorders. Activated microglia and secreted factors such as tumor necrosis factor-alpha (TNFα) are key mediators of neuroinflammation and may contribute to neuronal dysfunction. The main aim of this study was to evaluate the therapeutic efficacy of intranasal cationic nanoemulsions encapsulating an anti-TNFα siRNA, for potential anti-inflammatory therapy, tested in an LPS induced model of neuroinflammation. The strategy of developing a cationic nanoemulsion system for silencing the TNFα gene was to efficiently provide neuroprotection against inflammation. TNFα siRNA nanoemulsions were prepared and characterized for particle size, surface charge, morphology, and stability and encapsulation efficiency. Qualitative and quantitative intracellular uptake studies by confocal imaging and flow cytometry, respectively, showed higher uptake compared to Lipofectamine® transfected siRNA. Nanoemulsions showed significantly lower (p<0.01) levels of TNFα in LPS-stimulated cells. Upon intranasal delivery of cationic nanoemulsions almost 5 fold higher uptake was observed in the rat brain compared to non-encapsulated siRNA. More importantly, intranasal delivery of TNFα siRNA nanoemulsions in vivo markedly reduced...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research