NDLI: Nanoparticle delivery of RNA-based therapeutics to alter the vocal fold tissue response to injury.

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Nanoparticle delivery of RNA-based therapeutics to alter the vocal fold tissue response to injury.

Content Provider	Semantic Scholar
Author	Hiwatashi, Nao Kraja, Iv Benedict, Peter A. Dion, Gregory R. Bing, Renjie Rousseau, Bernard Amin, Milan R. Nalband, Danielle M. Kirshenbaum, Kent Branski, Ryan C.
Copyright Year	2018
Abstract	OBJECTIVES/HYPOTHESIS Our laboratory and others hypothesized that Smad3 is a principle mediator of the fibrotic phenotype in the vocal folds (VFs), and we further posited that alteration of Smad3 expression through short interfering (si)RNA holds therapeutic promise, yet delivery remains challenging. To address this issue, we employed a novel synthetic oligomer, lipitoid, complexed with siRNA to improve stability and cellular uptake with the goal of increased efficiency of RNA-based therapeutics. STUDY DESIGN In vitro study and in vivo animal model. METHODS In vitro, lipitoid cytotoxicity was quantified via colorimetric and LIVE/DEAD assays in immortalized human VF fibroblasts and primary rabbit VF fibroblasts. In addition, optimal incubation interval and solution for binding siRNA to lipitoid for intracellular delivery were determined. In vivo, a rabbit model of VF injury was employed to evaluate Smad3 knockdown following locally injected lipitoid-complexed siRNA. RESULTS In vitro, lipitoid did not confer additional toxicity compared to commercially available reagents. In addition, 20-minute incubation in 1× phosphate-buffered saline resulted in maximal Smad3 knockdown. In vivo, Smad3 expression increased following VF injury. This response was significantly reduced in injured VFs at 4 and 24 hours following injection (P = .035 and .034, respectively). CONCLUSIONS The current study is the first to demonstrate targeted gene manipulation in the VFs as well as the potential utility of lipitoid for localized delivery of genetic material in vivo. Ideally, these data will serve as a platform for future investigation regarding the functional implications of therapeutic gene manipulation in the VFs. LEVEL OF EVIDENCE NA. Laryngoscope, 128:E178-E183, 2018.
File Format	PDF HTM / HTML
DOI	10.1002/lary.27047
Alternate Webpage(s)	http://sbccp.org.br/arquivos/LG2018-05/45.pdf
PubMed reference number	29238989
Alternate Webpage(s)	https://doi.org/10.1002/lary.27047
Journal	Medline
Volume Number	128
Issue Number	5
Journal	The Laryngoscope
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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