title: Biokinetic studies of non-complexed siRNA versus nano-sized PEI F25-LMW/siRNA polyplexes following intratracheal instillation into mice.
abstract: Successful 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.
authors.affiliation: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, Germany; Philipps-University of Marburg, Department of Pharmaceutics and Biopharmacy, Ketzerbach 63, 35037 Marburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Lipka
authors.affiliation: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Semmler-Behnke
authors.affiliation: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Wenk
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology (IZI) Leipzig, Perlickstraße 1, 04103 Leipzig, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Burkhardt
authors.affiliation: Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, University of Leipzig, Haertelstrasse 16-18, 04107 Leipzig, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Aigner
authors.affiliation: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstaedter Landstraße 1, 85764 Neuherberg, Germany. Electronic address: kreyling@helmholtz-muenchen.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kreyling
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018014:Gene Transfer Techniques; D008156:Luciferases / Q000235:genetics; D008297:Male; D008819:Mice, Nude; D008970:Molecular Weight; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D034741:RNA, Small Interfering; D011094:Polyethyleneimine; D008156:Luciferases
keywords: Biokinetics; Lung therapy; Radiolabeled polyethyleneimine (PEI)/siRNA polyplexes