NFkappaB decoy, double stranded
oligonucleotides containing NFkappaB binding sequences, inhibits NFkappaB-mediated production of inflammatory
cytokines, and therefore NFkappaB decoy has been applied to several diseases. However, naked NFkappaB decoy, which is quickly cleared from the circulation in mice after
intravenous injection, is readily absorbed into the systemic circulation. In order to deliver enough NFkappaB decoy for a
therapeutic effect, it is necessary to develop a carrier, which enables much more NFkappaKB decoy to transfer to the target cells. In this study, using N-[1-(2,3-dioleyloxy)propyl]-n,n,n-trimethylammonium
chloride (
DOTMA)/
cholesterol (1 :1)
liposomes, the
therapeutic effect of NFkappaB decoy was investigated in an LPS induced acute
hepatitis model mice. The mean diameter of the cationic
liposomes/NFkappaB decoy complex was about 70.9 nm and the zeta potential of complex was about 37.4 mV. Tissue distribution was determined by measuring the radioactivity of a cationic
liposomes/ [32P] NFkappaB decoy complex after
intravenous injection. The cationic
liposomes/[32P] NFkappaB decoy complex was rapidly accumulated in the lung and gradually moved to the liver. The
therapeutic effect was determined by the serum concentration of
TNFalpha in LPS treated mice. The production of
TNFalpha was significantly inhibited by cationic
liposomes/NFkappaB decoy complex but not by cationic
liposomes/random decoy complex or naked NFkappaB decoy. These results suggested that NFkappaB decoy
therapy could be achieved using cationic
liposomes. This information is of great value for the design of NFkappaB decoy carrier systems.