Mouse Interferon-γ in Liposomes: Pharmacokinetics,Organ-Distribution,and Activation of Spleen and Liver Macrophages In Vivo

Abstract

Recombinant mouse interferon-γ (IFN-γ) was encapsulated into multilamellar vesicles and the proportion of encapsulated IFN-γ determined by biological activity was 19%. The distribution of ¹²⁵I-labeled IFN-γ liposomes in C57BL/6 mice was analyzed. After an initial enrichment of liposomes in lung, more than 60% of total ¹²⁵I-labeled IFN-γ was accumulated in spleen and liver. Furthermore, it was observed if the encapsulation of IFN-γ in liposomes prevented the rapid decay of IFN-γ in serum of C57BL/6 mice after intravenous injection. We compared the serum decay curve of liposomal and free IFN-γ, and showed that IFN-γ encapsulated in liposomes has an elongated availability in the serum. In addition, we established that a combination of 10² U/ml IFN-γ and 1 μg/ 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-γ (5 × 10³ U) and muramyltripeptide (MTP-PE) (6 μg) 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.