The effect of intracellular delivery of catalase and antisense oligonucleotides to NF-κB using albumin microcapsules in the endotoxic shock model

Microencapsulated (MC) catalase has been shown to inhibit H2O2 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.