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https://hdl.handle.net/2440/109906
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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 1530-8022 |
Statement of Responsibility: | 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 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1002009 |
Published version: | http://dx.doi.org/10.1177/0885328215579422 |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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