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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 möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 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
Zeitschrift International Journal of Pharmaceutics
Quellenangaben Band: 500, Heft: 1-2, Seiten: 227-235 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Begutachtungsstatus