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

International Journal of Pharmaceutics
Jens LipkaWolfgang Kreyling

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.

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Citations

Sep 23, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yingshan QiuWanling Liang
Sep 21, 2018·Expert Opinion on Drug Delivery·Mariana MagalhãesFrancisco Veiga
Jan 25, 2020·Nanomaterials·Jorge F Pontes, Ana Grenha
May 28, 2017·International Journal of Pharmaceutics·Elizabeth BielskiSandro R P da Rocha
Jun 5, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Nidhi RavalRakesh K Tekade

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