In-vitro antileishmanial and trypanocidal activities of arsonoliposomes and preliminary in-vivo distribution in BALB/c mice.
We have studied the antiprotozoal activity of some recently prepared and characterized arsonoliposome formulations. Plain arsonoliposomes and phosphatidylcholine arsonoliposomes prepared with palmitoyl- (C16) or lauroyl-(C12) acyl side chain arsonolipids showed in-vitro antileishmanial activity after a 72-h incubation period against wild-type promastigote forms of Leishmania donovani. The IC50 values ranged from 0.40 to 11.6 microM arsonolipid. Interestingly, all preparations tested were found to be significantly more potent against amphotericin B- or miltefosine-resistant promastigote forms of L. donovani, with IC50 values ranging between 0.21- and 2.33 microM arsonolipid. When tested in-vitro against Trypanosoma brucei brucei, all arsonoliposome formulations were found to have anti-trypanosomal activity after a 24-h incubation period. The fact that the corresponding arsonolipids (dissolved in dimethyl sulfoxide) were found not to be potent against the Leishmania promastigotes or the trypanosomes tested suggested that the formation of liposomes possibly influenced the mode of interaction between the active lipid and the parasites modulating their potency. In addition, a preliminary in-vivo study in BALB/c mice was performed for the initial evaluation of the biodistribution of arsonoliposomes. The accumulation of arsenic in the BALB/c mouse liver in relatively high amounts was an additional advantage of this approach for anti-protozoal therapy, especially for visceral leishmaniasis where parasites are located mainly in the liver.
Antimisiaris
Sophia G
SG
Department of Pharmacy, Laboratory of Pharmaceutical Technology, University of Patras, Rio 26500, Greece. S.Antimisiaris@upatras.gr
Ioannou
Panayiotis V
PV
Loiseau
Philippe M
PM
D000818:Animals; D001152:Arsenicals / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D007891:Leishmania / Q000187:drug effects* / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D014344:Trypanocidal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000378:metabolism
D001152:Arsenicals; D008081:Liposomes; D014344:Trypanocidal Agents; D002784:Cholesterol