Intranasal brain delivery of cationic nanoemulsion-encapsulated TNF? siRNA in prevention of experimental neuroinflammation.

ABSTRACT: Neuroinflammation is a hallmark of acute and chronic neurodegenerative disorders. The main aim of this study was to evaluate the therapeutic efficacy of intranasal cationic nanoemulsion encapsulating an anti-TNF? siRNA, for potential anti-inflammatory therapy. TNF? 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. Nanoemulsion significantly lowered TNF? levels 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 TNF? siRNA nanoemulsions in vivo markedly reduced the unregulated levels of TNF? in an LPS-induced model of neuroinflammation. These results indicate that intranasal delivery of cationic nanoemulsions encapsulating TNF? siRNA offered an efficient means of gene knockdown and this approach has significant potential in prevention of neuroinflammation.Neuroinflammation is often seen in patients with neurodegenerative disorders and tumor necrosis factor-alpha (TNF?) plays a significant role in contributing to neuronal dysfunction. As a result, inhibition of TNF? may alleviate disease severity. In this article, the authors investigated using a cationic nanoemulsion system carrying TNF? siRNA intra-nasally to protect against neuroinflammation. This new method may provide a future approach in this clinical setting.

SUBMITTER: Yadav S 

PROVIDER: S-EPMC4837036 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature