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Lipka, J. ; Semmler-Behnke, M. ; Wenk, A. ; Burkhardt, J.* ; Aigner, A.* ; Kreyling, W.G.

Biokinetic studies of non-complexed siRNA versus nano-sized PEI F25-LMW/siRNA polyplexes following intratracheal instillation into mice.

Int. J. Pharm. 500, 227-235 (2016)

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Open Access Green as soon as Postprint is submitted to ZB.

Abstract
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Succesful gene therapy requires stability and sufficient bioavailability of the applied drug at the site of action. In the case of RNA interference (RNAi), non-viral vectors play a promising role for delivering intact siRNA molecules. We selected a low molecular weight polyethyleneimine (PEI F25-LMW) and investigated the biokinetics of PEI F25-LMW/siRNA polyplexes in comparison to non-complexed siRNA molecules upon intratracheal application into mice. Additionally, a bronchoalveolar lavage was performed to locate the siRNA within the different lung compartments and to analyse possible inflammatory reactions. Liquid scintillation counting of a 32P-label was used to follow the siRNA within the whole body. During the complete observation time more than 75% of the applied dose was found at the target site. The complexation with PEI F25- LMW prevented the siRNA from being degraded and cleared and prolonged its retention time. A low inflammatory reaction was observed on the basis of cell differentiation. Taken together, PEI F25-LMW meets fundamental requirements on non-viral vectors for local pulmonary siRNA delivery.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Biokinetics ; Lung Therapy ; Radiolabeled Polyethyleneimine (pei)/sirna Polyplexes; Low-molecular-weight; In-vivo; Gene-therapy; Transfection Efficiency; Chemical-modification; Rna Degradation; Polyethylenimine; Delivery; Lung; Biodistribution

ISSN (print) / ISBN 0378-5173

e-ISSN 1873-3476

Journal International Journal of Pharmaceutics

Quellenangaben Volume: 500, Issue: 1-2, Pages: 227-235

Publisher Elsevier

Publishing Place Amsterdam

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Lung Health and Immunity (LHI)