Intranasal brain delivery of cationic nanoemulsion-encapsulated TNFα siRNA in prevention of experimental neuroinflammation

Nanomedicine : Nanotechnology, Biology, and Medicine
Sunita YadavMansoor Amiji

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-TNFα siRNA, for potential anti-inflammatory therapy. 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. Nanoemulsion significantly lowered TNFα 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 TNFα siRNA nanoemulsions in vivo markedly reduced the unregulated levels of TNFα in an LPS-induced model of neuroinflammation. 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. Neuroinflammation is often seen in patients with n...Continue Reading

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Citations

Oct 21, 2016·Redox Biology·Calina BetlazarGuo-Jun Liu
Jan 28, 2017·Colloids and Surfaces. B, Biointerfaces·Giovanna RassuElisabetta Gavini
Apr 1, 2017·Therapeutic Delivery·Palpandi PandiWahid Khan
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Oct 26, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Wei ChenZahid Hussain

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