PT  - JOURNAL ARTICLE
AU  - Wijagkanalan, Wassana
AU  - Higuchi, Yuriko
AU  - Kawakami, Shigeru
AU  - Teshima, Mugen
AU  - Sasaki, Hitoshi
AU  - Hashida, Mitsuru
TI  - Enhanced Anti-Inflammation of Inhaled Dexamethasone Palmitate Using Mannosylated Liposomes in an Endotoxin-Induced Lung Inflammation Model
AID  - 10.1124/mol.108.050153
DP  - 2008 Nov 01
TA  - Molecular Pharmacology
PG  - 1183--1192
VI  - 74
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/74/5/1183.short
4100  - http://molpharm.aspetjournals.org/content/74/5/1183.full
SO  - Mol Pharmacol2008 Nov 01; 74
AB  - Inhalation of bacterial endotoxin induces pulmonary inflammation by activation of nuclear factor κB (NFκB), production of cytokines and chemokines, and neutrophil activation. Although glucocorticoids are the drugs of choice, administration of free drugs results in adverse effects as a result of a lack of selectivity for the inflammatory effector cells. Because alveolar macrophages play a key role in the inflammatory response in the lung, selective targeting of glucocorticoids to alveolar macrophages offers efficacious pharmacological intervention with minimal side effects. We have demonstrated previously the selective targeting of mannosylated liposomes to alveolar macrophages via mannose receptor-mediated endocytosis after intratracheal administration. In this study, the anti-inflammatory effects of dexamethasone palmitate incorporated in mannosylated liposomes (DPML) at 0.5 mg/kg via intratracheal administration were investigated in lipopolysaccharide-induced lung inflammation in rats. DPML significantly inhibited tumor necrosis factor α, interleukin-1β, and cytokine-induced neutrophil chemoattractant-1 levels, suppressed neutrophil infiltration and myeloperoxidase activity, and inhibited NFκB and p38 mitogen-activated protein kinase activation in the lung. These results prove the value of inhaled mannosylated liposomes as powerful targeting systems for the delivery of anti-inflammatory drugs to alveolar macrophages to improve their efficacy against lung inflammation. The American Society for Pharmacology and Experimental Therapeutics