Targeting of parasite-specific immunoliposome-encapsulated doxorubicin in the treatment of experimental visceral leishmaniasis.
A parasite-specific 51-kDa protein has been isolated from the membrane of macrophages infected with Leishmania donovani, the causative agent of visceral leishmaniasis. Active targeting of doxorubicin to infected macrophages was studied by incorporating it in immunoliposomes prepared by grafting F(ab)'(2) of anti-51-kDa antibody onto the liposomal surface. In a 45-day mouse model of visceral leishmaniasis, complete elimination of spleen parasite burden was achieved by doxorubicin incorporated in immunoliposome (immunodoxosome) at a dose of 250 microg/kg/day that was given for 4 consecutive days. A similar dose of free and liposomal drug (doxosome) had 45% and 84% parasite suppressive effects, respectively. Immunodoxosome and doxosome were generally less toxic than the free drug, as determined by several clinical parameters of cardiotoxicity and liver toxicity. These results not only indicate the potential of doxorubicin as an effective chemotherapeutic agent but also establish the use of immunoliposomes as drug carrier in the therapy of leishmaniasis.
Mukherjee
Snigdha
S
Molecular Cell Biology Laboratory, Indian Institute of Chemical Biology, Calcutta, India.
Das
Lopamudra
L
Kole
Labanyamoy
L
Karmakar
Sudipan
S
Datta
Neeta
N
Das
Pijush K
PK
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000633:toxicity; D004337:Drug Carriers; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008081:Liposomes; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000276:immunology / Q000302:isolation & purification
D000913:Antibodies, Protozoan; D004337:Drug Carriers; D007140:Immunoglobulin Fab Fragments; D008081:Liposomes; D015800:Protozoan Proteins; D004317:Doxorubicin