Interferon gamma in multilamellar visicles as therapeutic drug in experimental visceral leishmaniasis

Leishmaniasis is caused by an intracellular protozoan parasite. We examined the efficiency of immunotherapy with recombinant interferon gamma (IFN Gamma) in visceral leishmaniasis. In order to avoid the side effects encountered after the in vivo administration of high dosages of free IFN Gamma we encapsulated IFN Gamma and muramyltripeptide (MTP- PE) into multilamellar liposomes. The distribution of high123 J labelled IFN Gamma liposomes in C57BL/6 mice was investigated. We established that a combination of 5x10high3 U IFN Gamma and 6 Myg MTP- PE, encapsulated in liposomes, activates macrophages from spleen and liver in vivo to kill Leishmania donovani in vitro. For verification of these results in an in vivo infection model, susceptible mice were infected with Leishmania donovani and were treated with IFN Gamma and MTP-PE, encapsulated in multilamellar vesicles. Treatment consisted of multiple intravenous injections beginning prophylactic, simultaneously with the infec- tion and at va rious times of the exacerbation and remission phase. The targetting of the multilamellar vesicles to liver and spleen make them particularly suited for the delivery of macrophage activating substances used for treatment of Leishmania donovani infection. Mice treated with IFN Gamma and MTP-PE in liposomes had significantly fewer splenic parasites than the control groups.