Intravenous administration of mannosylated cationic liposome/NFkappaB decoy complexes effectively prevent LPS-induced cytokine production in a murine liver failure model.
The purpose of this study was to inhibit endotoxin induced cytokines production and liver injury by liver non-parenchymal cell (NPC) selective delivery of nuclear factor kappaB (NFkappaB) decoy using mannosylated cationic liposomes (Man-liposomes). In this study, we examined the distribution, inhibitory effect on cytokines production and ALT/AST of intravenously injected Man-liposome/NFkappaB decoy complex. Man-liposome/[(32)P] NFkappaB decoy complexes mostly accumulated in the liver, preferentially in NPC. In a murine lipopolysaccharide-induced liver failure model, the production of tumor necrosis factor-alpha (TNFalpha), IFNgamma, IL1-beta, ALT and AST were effectively reduced by Man-liposome complexes. However, cationic or galactosylated cationic liposome complexes could not inhibit TNFalpha production.
Higuchi
Yuriko
Y
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Kawakami
Shigeru
S
Oka
Machiko
M
Yabe
Yoshiyuki
Y
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D002412:Cations / Q000737:chemistry; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry*; D008099:Liver / Q000293:injuries; D017093:Liver Failure / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008358:Mannose / Q000737:chemistry*; D051379:Mice; D016328:NF-kappa B / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D010316:Particle Size
D002412:Cations; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008081:Liposomes; D016328:NF-kappa B; D008358:Mannose