Mouse interferon gamma in liposomes - Pharmacokinetics, organ-distribution, and activation of spleen and liver macrophages in vivo

Recombinant mouse interferon gamma (IFN y) was encapsulated into multilamellar vesicles and the proportion of encapsulated IFN y determined by biological activity was 19%. The distribution of 125 J labelled IFN y liposomes in C57BL/6 mice was analysed. After an initial enrichment of liposomes in lung more than 60% of total 125 J IFN y was accumulated in spleen and liver. Furthermore it was observed if the encapsulation of IFN y in liposomes prevented the rapid decay of IFN y in serum of C57BL/6 mice after intravenous injection. We compared the serum decay curve of liposomal and free IFN y and it is shown that IFN y encapsulated in liposomes has an elongated availability in the serum. In addition we established that a combination of 10 high 2 U/ml IFN y and 1 ug/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 y (5 x 10 high 3 U) and MTP-PE (6 ug) 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.