Intranasal brain delivery of cationic nanoemulsion-encapsulated TNFα siRNA in prevention of experimental neuroinflammation.
Intranasal brain delivery of cationic nanoemulsion-encapsulated TNFα siRNA in prevention of experimental neuroinflammation.
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DOI：
10.1016/j.nano.2015.12.374
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Amiji MM
中科院分区：
文献类型：
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作者：
Yadav S;Gandham SK;Panicucci R;Amiji MM
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 the unregulated levels of TNFα in an LPS-induced model of neuroinflammation where TNFα functions as a signaling molecule, which aggravates inflammation. These results indicate that intranasal delivery of cationic nanoemulsions encapsulating TNFα siRNA offered an efficient means of gene knockdown and this approach has significant potential in prevention of neuroinflammation.
