Visceral leishmaniasis: drug carrier system characteristics and the ability to clear parasites from the liver, spleen and bone marrow in Leishmania donovani infected BALB/c mice.
The efficacy of various sodium stibogluconate formulations against Leishmania donovani has been investigated using a BALB/c mouse model of visceral leishmaniasis. Only one therapy, multiple dosing with drug loaded sonicated vesicles, liposomes or niosomes, was found to be effective against parasites in the liver, spleen and bone marrow. Other treatments significantly reduced parasite liver burdens but either failed to effect spleen and bone marrow parasites, or were effective but toxic. Prophylactic treatment with sodium stibogluconate preparations, six days before infection, reduced parasite multiplication in the liver (free, niosomal and liposomal drug) and the spleen (sonicated, drug loaded niosomes only), but had no suppressive effect on bone marrow parasite burdens compared with controls. These results indicate that in-vivo sodium stibogluconate persists in some compartments at parasiticidal concentrations and that failure to reach this concentration at some sites of infection such as bone marrow, is the cause of treatment failure and relapse.
Carter
K C
KC
Immunology Division, Todd Centre, Strathclyde University, Glasgow, UK.
Dolan
T F
TF
Alexander
J
J
Baillie
A J
AJ
McColgan
C
C
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000378:metabolism; D000818:Animals; D000967:Antimony Sodium Gluconate / Q000008:administration & dosage / Q000494:pharmacology*; D001853:Bone Marrow / Q000469:parasitology*; D002626:Chemistry, Pharmaceutical; D005260:Female; D005942:Gluconates / Q000494:pharmacology*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D008099:Liver / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000469:parasitology*
D005942:Gluconates; D015060:1,2-Dipalmitoylphosphatidylcholine; D000967:Antimony Sodium Gluconate