The effect of intracellular delivery of catalase and antisense oligonucleotides to NF-κB using albumin microcapsules in the endotoxic shock model
AbstractMicroencapsulated (MC) catalase has been shown to inhibit H 2 O 2 and tumor necrosis factor (TNF) in vitro after endotoxin stimulation. It is the purpose of this study to determine whether MC catalase improves pro-inflammatory cytokine inhibition and mortality in an endotoxic shock model in vivo . We also examined whether MC catalase and antisense oligonucleotides (ASO) to nuclear factor κB (NF-κB) together improved survival by inhibiting pro-inflammatory cytokines using different mechanisms. Methods : Albumin microcapsules containing catalase and ASO to NF-κB were prepared 2–7 μm in size by using a Büchi spray dryer. Progressively increasing doses of MC catalase, MC ASO to NF-κB, and the combination were given to rats before the administration of Escherichia coli endotoxin. Results demonstrated 60% survival in rats given 15 mg/kg MC catalase, 70% survival with 20 mg/kg MC ASO NF-κB, and 80% survival with the combination. TNF was inhibited by 53% in the MC catalase group 4 h after endotoxin administration, 43% in the ASO NF-κB group, and 78% in the combination group compared to controls. In conclusion , this study demonstrates the effectiveness of MC intracellular delivery of the naturally occurring antioxidant catalase in improving animal survival. The addition of ASO to NF-κB improved both cytokine inhibition and animal survival in endotoxic shock.