id author title date pages extension mime words sentences flesch summary cache txt cord-351310-6p42b144 Bohr, Adam Treatment of acute lung inflammation by pulmonary delivery of anti-TNF-α siRNA with PAMAM dendrimers in a murine model 2020-08-13 .txt text/plain 4342 263 56 In this study, commercially available generation 3 poly(amidoamine) (PAMAM) dendrimer was investigated for pulmonary delivery of siRNA directed against tumor necrosis factor (TNF) α for the treatment of acute lung inflammation. Delivery efficiency was assessed in vitro in the RAW264.7 macrophage cell line activated with lipopolysaccharide (LPS), and efficacy was evaluated in vivo in a murine model of LPS-induced lung inflammation upon pre-treatment with TNF-α siRNA. Also in vivo, the PAMAM dendriplexes induced efficacious TNF-α siRNA inhibition, as compared to non-complexed siRNA, upon pulmonary administration to mice with LPS-induced lung inflammation. In this study, we investigated generation 3 PAMAM dendrimers as transfection agents for pulmonary delivery of siRNA targeting TNF-α and examined their efficacy and safety in a murine acute lung inflammation model. Generation 3 PAMAM dendrimers were selected because they display very good efficiency for dendriplex formation They were prepared at different dendrimer-siRNA ratios and were characterized in vitro and in vivo concerning complexation, cellular uptake, cytotoxicity, in vitro transfection efficiency and in vivo therapeutic efficacy at the RNA and protein levels, respectively. ./cache/cord-351310-6p42b144.txt ./txt/cord-351310-6p42b144.txt