Mouse interferon-gamma in liposomes: pharmacokinetics, organ-distribution, and activation of spleen and liver macrophages in vivo.
Recombinant mouse interferon-gamma (IFN-gamma) was encapsulated into multilamellar vesicles and the proportion of encapsulated IFN-gamma determined by biological activity was 19%. The distribution of 125I-labeled IFN-gamma liposomes in C57BL/6 mice was analyzed. After an initial enrichment of liposomes in lung, more than 60% of total 125I-labeled IFN-gamma was accumulated in spleen and liver. Furthermore, it was observed if the encapsulation of IFN-gamma in liposomes prevented the rapid decay of IFN-gamma in serum of C57BL/6 mice after intravenous injection. We compared the serum decay curve of liposomal and free IFN-gamma, and showed that IFN-gamma encapsulated in liposomes has an elongated availability in the serum. In addition, we established that a combination of 10(2) U/ml IFN-gamma and 1 microgram/ml MTP-PE, encapsulated in liposomes, activates splenic and starch-elicited peritoneal macrophages in vitro synergistically to kill Leishmania donovani promastigotes. After intravenous injection of liposomal IFN-gamma (5 X 10(3) U) and muramyltripeptide (MTP-PE) (6 micrograms) in C57BL/6 mice, splenic and liver macrophages were activated in vivo to kill Leishmania species in vitro. Neither an injection of the same amount of free substances nor injection of empty liposomes resulted in an increased leishmanicidal activity.
Hockertz
S
S
Department of Immunology, Fraunhofer Institute for Toxicology and Aerosol Research, Hannover, FRG.
Franke
G
G
Kniep
E
E
Lohmann-Matthes
M L
ML
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004337:Drug Carriers; D004357:Drug Synergism; D005260:Female; D007371:Interferon-gamma / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D007898:Leishmaniasis, Visceral / Q000628:therapy; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000276:immunology; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010714:Phosphatidylethanolamines / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D014018:Tissue Distribution
D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011994:Recombinant Proteins; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma