Trypanocidal activity of arsonoliposomes: effect of vesicle lipid composition.
Sonicated arsonoliposomes were prepared using an arsonolipid with palmitic acid acyl chain (C16), mixed with phosphatidylcholine (PC-based) or 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC-based), and cholesterol (Chol) with a molar ratio C16 /PC or DSPC/ Chol 8:12:10. PEG-lipid (1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated to polyethylenoglycol 2000) containing vesicles (pegylated-arsonoliposomes) were also prepared. The in vitro and in vivo trypanocidal activity of the various types of arsonoliposomes was evaluated. Although PC-based arsonoliposomes exhibited in vivo activity on an acute trypanosomiasis animal model, no evidence of activity was demonstrated for DSPC-based or pegylated-arsonoliposomes on a chronic model. Despite the fact that DSPC-based and pegylated-arsonoliposomes have better bioavailability compared to PC-based ones, their in vitro activity is lower than that of PC-based arsonoliposomes, indicating the importance of arsonoliposome lipid composition on their trypanocidal activity and suggesting that further arsonoliposome structure design is required to overcome these disadvantages.
Zagana
Paraskevi
P
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26500, Greece.
Klepetsanis
Pavlos
P
Ioannou
Panayiotis V
PV
Loiseau
Philippe M
PM
Antimisiaris
S G
SG
D000818:Animals; D018053:Arsenites / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D002784:Cholesterol; D066298:In Vitro Techniques; D008081:Liposomes; D051379:Mice; D010168:Palmitates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000378:metabolism; D014352:Trypanosomiasis / Q000188:drug therapy
C526368:2,3-dipalmitoyloxypropylarsonic acid; D018053:Arsenites; C102564:DPPE-PEG2000; D008081:Liposomes; D010168:Palmitates; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D014344:Trypanocidal Agents; D011092:Polyethylene Glycols; D002784:Cholesterol; C010942:1,2-distearoyllecithin