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Type: Journal article
Title: In vivo delivery of functional Flightless I siRNA using layer-by-layer polymer surface modification
Author: Martens, P.
Ly, M.
Adams, D.
Penzkover, K.
Strudwick, X.
Cowin, A.
Poole-Warren, L.
Citation: Journal of Biomaterials Applications, 2015; 30(3):257-268
Publisher: SAGE Publications
Issue Date: 2015
ISSN: 0885-3282
Statement of
Penny J Martens, Mai Ly, Damian H Adams, Kathryn R Penzkover, Xanthe Strudwick, Allison J Cowin, and Laura A Poole-Warren
Abstract: Gene silencing using small interfering RNA has been proposed as a therapy for cancer, viral infections and other diseases. This study aimed to investigate whether layer-by-layer polymer surface modification could deliver small interfering RNA to decrease fibrotic processes associated with medical device implantation. Anti-green fluorescent protein labelled small interfering RNA was applied to tissue culture plates and polyurethane using a layer-by-layer technique with small interfering RNA and poly-L-lysine. In vitro studies showed that the level of down-regulation of green fluorescent protein was directly related to the number of coatings applied. This layer-by-layer coating technique was then used to generate Rhodamine-Flii small interfering RNA-coated implants for in vivo studies of small interfering RNA delivery via subcutaneous implantation in mice. After two days, Rh-positive cells were observed on the implants' surface indicating cellular uptake of the Rhodamine-Flii small interfering RNA. Decreased Flii gene expression was observed in tissue surrounding the Rhodamine-Flii small interfering RNA coated implants for up to seven days post implantation, returning to baseline by day 21. Genes downstream from Flii, including TGF-β1 and TGF-β3, showed significantly altered expression confirming a functional effect of the Rhodamine-Flii small interfering RNA on gene expression. This research demonstrates proof-of-principle that small interfering RNA can be delivered via layer-by-layer coatings on biomaterials and thereby can alter the fibrotic process.
Keywords: Animal model; drug delivery; polyurethane; siRNA
Rights: © The Author(s) 2015
DOI: 10.1177/0885328215579422
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