Open Access Green as soon as Postprint is submitted to ZB.
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)
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.
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
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
Quellenangaben Volume: 500, Issue: 1-2, Pages: 227-235
Publishing Place Amsterdam
Institute(s) Institute of Lung Biology (ILBD)