Document Detail


Intratracheally instilled mannosylated cationic liposome/NFκB decoy complexes for effective prevention of LPS-induced lung inflammation.
MedLine Citation:
PMID:  20035809     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The nuclear factor kappa B (NFκB) signaling pathway is a key mechanism in the pathophysiology of lung inflammation. NFκB is critically responsible for the expression of pro-inflammatory mediators following activation. The specific inhibition of NFκB by a NFκB decoy via inhalation appears to improve therapeutic effects. However, administration of naked NFκB 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 NFκB decoy by mannosylated (Man) cationic liposomes in a LPS-induced lung inflammation model after intratracheal administration. The complex of Man-cationic liposome/NFκB decoy was physically stable during spraying. Man-cationic liposome/NFκB decoy complex was selectively delivered to alveolar macrophages for subsequent localization of NFκB 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/50μg NFκB decoy complex significantly inhibited the release of TNF-α, IL-1β and CINC-1, neutrophil infiltration and NFκB activation compared with naked NFκB decoy, cationic liposome/NFκB decoy complex and Man-cationic liposome/scrambled decoy complex treatments. This study demonstrates the sufficient targeting of NFκB decoy using Man-cationic liposomes in a novel effective anti-inflammatory therapy for lung inflammation.
Authors:
Wassana Wijagkanalan; Shigeru Kawakami; Yuriko Higuchi; Fumiyoshi Yamashita; Mitsuru Hashida
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-24
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  149     ISSN:  1873-4995     ISO Abbreviation:  J Control Release     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  42-50     Citation Subset:  IM    
Copyright Information:
Copyright © 2009 Elsevier B.V. All rights reserved.
Affiliation:
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
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