Coenzyme Q10 in vesicles composed of archaeal ether lipids or conventional lipids enhances the immuno-adjuvanticity to encapsulated protein.
Cellular accumulation, tissue distribution, and immuno-adjuvanticity were evaluated for liposomal CoQ10 prepared from either distearoylphosphatidylcholine:dicetylphosphate:cholesterol (4:1:5, mol. ratio) (conventional liposomes) or from the total polar lipids of the archaeon Methanosarcina mazei (archaeosomes). Liposomal CoQ10 vesicles of approximately 100 nm diameter, containing up to 179 mumol of CoQ10 per mg of lipid have been evaluated using J774A.1 macrophages and Balb/c mice. Archaeosomes uptake by J774A.1 macrophages was better than with the conventional liposome, and the incorporation of CoQ10 enhanced the uptake of both lipid vesicle types. All vesicle types were detected in the liver and spleen of mice (4-27% of injected dose) within 3 h of intraperitoneal injection. Moreover, incorporation of CoQ10 into lipid vesicles enhanced the immuno-adjuvanticity of both conventional liposomes and archaeosomes, to achieve approximately a doubling in the titres of BSA-specific antibody in sera to 169 and 430 micrograms ml-1, respectively. Increases in IgG1 and IgG2a/2b accounted for most of the CoQ10-induced increases in anti-BSA titres. These results are rationalized on the basis of surface hydrophobicity and opsonization changes induced by the presence of CoQ10 in vesicles. We suggest that liposomal CoQ10 has potential as a new generation of vaccine delivery system to enhance the immune response. Its use as a novel delivery system may be particularly effective under pathological conditions where the occurrence of an oxidative stress condition significantly impairs the immune system functions.
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada.
B
B
Makabi-Panzu
G D
GD
Sprott
G B
GB
Patel
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000097:blood; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003067:Coenzymes; D004337:Drug Carriers; D004987:Ethers / Q000737:chemistry; D005260:Female; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism; D017019:Methanosarcinaceae / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D013499:Surface Properties; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology
D000276:Adjuvants, Immunologic; D001798:Blood Proteins; D003067:Coenzymes; D004337:Drug Carriers; D004987:Ethers; D008055:Lipids; D008081:Liposomes; D014451:Ubiquinone; C024989:coenzyme Q10