Back to Search
Start Over
Intratracheally instilled mannosylated cationic liposome/NFκB decoy complexes for effective prevention of LPS-induced lung inflammation.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2011 Jan 05; Vol. 149 (1), pp. 42-50. Date of Electronic Publication: 2009 Dec 24. - Publication Year :
- 2011
-
Abstract
- 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.<br /> (Copyright © 2009 Elsevier B.V. All rights reserved.)
- Subjects :
- Administration, Inhalation
Animals
Anti-Inflammatory Agents administration & dosage
Anti-Inflammatory Agents pharmacokinetics
Bronchoalveolar Lavage Fluid cytology
Bronchoalveolar Lavage Fluid immunology
Cations
Cells, Cultured
Cytokines immunology
Disease Models, Animal
Electrophoretic Mobility Shift Assay
Epithelial Cells drug effects
Epithelial Cells immunology
Epithelial Cells metabolism
Lipopolysaccharides toxicity
Liposomes
Lung immunology
Lung metabolism
Macrophages, Alveolar drug effects
Macrophages, Alveolar immunology
Macrophages, Alveolar metabolism
Male
Microscopy, Confocal
NF-kappa B immunology
Neutrophil Infiltration drug effects
Neutrophil Infiltration immunology
Oligodeoxyribonucleotides administration & dosage
Oligodeoxyribonucleotides pharmacokinetics
Peroxidase metabolism
Pneumonia immunology
Pneumonia metabolism
Rats
Rats, Wistar
Tissue Distribution
Anti-Inflammatory Agents therapeutic use
Lung drug effects
Mannose chemistry
NF-kappa B antagonists & inhibitors
Oligodeoxyribonucleotides therapeutic use
Pneumonia drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 149
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 20035809
- Full Text :
- https://doi.org/10.1016/j.jconrel.2009.12.016