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

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• 作者：Jens Lipka^a ; ^b ; Manuela Semmler-Behnke^a ; Alexander Wenk^a ; Jana Burkhardt^c ; Achim Aigner^d ; Wolfgang Kreyling^a ; ^{kreyling@helmholtz-muenchen.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Biokinetics ; Radiolabeled polyethyleneimine (PEI)/siRNA polyplexes ; Lung therapy
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：16 March 2016
• 年：2016
• 卷：500
• 期：1-2
• 页码：227-235
• 全文大小：1641 K

文摘

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.