Treatment of visceral leishmaniasis with sterically stabilized liposomes containing camptothecin.
The efficacy of 20(S)-camptothecin (CPT), free and incorporated into sterically stabilized liposomes, has been investigated in vitro against Leishmania donovani promastigotes and in vivo in a murine model of visceral leishmaniasis. Incubation of L. donovani promastigotes with free or liposomal CPT inhibited the growth of parasites in a dose-dependent manner. Tissue distribution studies revealed that the intraperitoneal administration of liposomal CPT was efficient for the delivery of high drug levels to the liver and spleen. Treatment of infected mice with intraperitoneal injections of free and liposomal CPT significantly reduced the parasite loads in the livers by 43 and 55%, respectively, compared with the loads for untreated controls. However, both treatments caused normochromic anemia and neutropenia.
Proulx
M E
ME
Centre de Recherche en Infectiologie, Université Laval, Québec, Québec, Canada.
Désormeaux
A
A
Marquis
J F
JF
Olivier
M
M
Bergeron
M G
MG
D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004355:Drug Stability; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D016896:Treatment Outcome
D000981:Antiprotozoal Agents; D004337:Drug Carriers; D008081:Liposomes; D002166:Camptothecin