Antileishmanial and trypanocidal activities of new miltefosine liposomal formulations.
Liposomes composed of hexadecylphosphocholine/egg phosphatidylcholine/stearylamine (HePC/EPC/SA) 10:10:0.1, 10:10:0.5 and 10:10:1 (molar ratio) (1-3) were prepared and lyophilized. The liposomes were physicochemically characterized (size and zeta-potential) and they were found stable at 4 degrees C over a period of 4 weeks. In vitro, liposomes 1 and 2 were about twice more active than HePC against Leishmania donovani WT whereas liposomes 3 were about three times more active than HePC on HePC-resistant promastigotes. Although liposomes 1-3 were inactive on the in vitro intramacrophage amastigote model, the ability of the liposomes to accumulate within the liver where parasites are located justifies a further in vivo evaluation. We observed that liposome 1 was twice more active than HePC against Trypanosoma brucei brucei bloodstream forms maintained in vitro. In vivo results showed that liposomal HePC seemed to be less toxic than the free drug despite the absence of significant antitrypanosomal activity.
Papagiannaros
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Department of Pharmaceutical Technology, School of Pharmacy, National and Kapodistrian University of Athens Panepistimiopolis, Zografou, 15771 Athens, Greece.
Bories
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Demetzos
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Loiseau
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PM
D000588:Amines / Q000737:chemistry; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014353:Trypanosomiasis, African / Q000188:drug therapy*
D000588:Amines; D008081:Liposomes; D010713:Phosphatidylcholines; D014344:Trypanocidal Agents; D010767:Phosphorylcholine; C039128:miltefosine; C009317:stearylamine