Targeting of mannosylated liposome incorporated benzyl derivative of Penicillium nigricans derived compound MT81 to reticuloendothelial systems for the treatment of visceral leishmaniasis

Abstract

The antileishmanial property of a Benzyl derivative of a new antibiotic MT81 (Bz₂MT81), isolated and purified from a fungal strain of Penicillium nigricans NRRL 917 was tested in free, liposome intercalated and mannose coated liposome intercalated forms in vivo against visceral leishmaniasis in hamsters. Mannose grafted liposome intercalated Bz₂MT81 eliminated intracellular amastigotes of Leishmania donovani within splenic macrophages more efficiently than the liposome intercalated Bz₂MT81 or free Bz₂MT81. At a dose equivalent to 7.5 μg/Kg body weight when injected subcutaneously (s.c) in mannose grafted liposome intercalated form for 15 days in an interval of three days, the splenic parasitic load decreased to the extent of 79.1% of the total parasite present in infected control animals. Whereas, an identical amount (7.5 μg/Kg body weight) of Bz₂MT81 in free or liposome intercalated form was found less effective in controlling the parasite in spleen (in free Bz₂MT81 form, suppression of parasitic load is 49.8% and in liposome intercalated form, it is 55.1%). Both mannosylated liposomes and Bz₂MT81 were noted non-toxic to the host peritoneal macrophages. Histological examinations of spleen and liver, kidney function tests (SGPT, alkaline phosphatase, creatinine and urea in blood plasma) showed that the toxicity of Bz₂MT81 was reduced up to normal level when mannose grafted liposomal Bz₂MT81 were administered.

Keywords: :

• Visceral leishmaniasis
• mannose grafted liposomes
• benzyl derivative of MT81; Histopathology
• Penicillium nigricans