Intratracheally instilled mannosylated cationic liposome/NFκB decoy complexes for effective prevention of LPS-induced lung inflammation

The nuclear factor kappa B (NF kappa B) signaling pathway is a key mechanism in the pathophysiology of lung inflammation. NF kappa B is critically responsible for the expression of pro-inflammatory mediators following activation. The specific inhibition of NF kappa B by a NF kappa B decoy via inhalation appears to improve therapeutic effects. However, administration of naked NF kappa B decoy limits the efficacy of the decoy strategy due to low targeting ability to immune cells such as alveolar macrophages. In this study, we have assessed the effect of alveolar macrophage-targeted NF kappa B decoy by mannosylated (Man) cationic liposomes in a LPS-induced lung inflammation model after intratracheal administration. The complex of Man-cationic liposome/NF kappa B decoy was physically stable during spraying. Man-cationic liposome/NF kappa B decoy complex was selectively delivered to alveolar macrophages for subsequent localization of NF kappa B decoy in the cytoplasm and to a lesser extent in the nucleus. In the LPS-induced lung inflammation model, pre-treatment with Man-cationic liposome/50 mu g NF kappa B decoy complex significantly inhibited the release of TNF-alpha, IL-1 beta and CINC-1, neutrophil infiltration and NF kappa B activation compared with naked NF kappa B decoy, cationic liposome/NF kappa B decoy complex and Man-cationic liposome/scrambled decoy complex treatments. This study demonstrates the sufficient targeting of NF kappa B decoy using Man-cationic liposomes in a novel effective anti-inflammatory therapy for lung inflammation. (C) 2009 Elsevier B.V. All rights reserved.