In vivo distribution of arsonoliposomes: effect of vesicle lipid composition.
Sonicated arsonoliposomes were prepared using arsonolipid with palmitic acid acyl chain (C16), mixed with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC-based), and cholesterol (Chol) with a molar ratio C16/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. DSPC-based and Pegylated-arsonoliposomes, were administered by intraperitoneal injection in balb/c mice (15 mg arsenic/kg) and the distribution of As in the organs was measured by atomic absorption spectroscopy. Results demonstrate that a high portion of the dose administered is rapidly excreted since 1 h post-injection only about 30-40% of the dose was detected cumulatively in animal tissues. After this, the whole body elimination of arsenic was a slow process with a half-life of 27.6 h for Pegylated-arsonoliposomes, and 83 h, for the DSPC-based ones. For both arsonoliposomes, arsenic distribution was greater in intestines, followed by liver, carcass+skin stomach, spleen, kidney, lung and heart. Different arsenic kinetics in blood between the two liposome types were observed. Compared to the results obtained previously with PC-based arsonoliposomes, both the DSPC-based and Pegylated-arsonoliposomes have better bioavailability. This proves that arsonoliposome lipid composition (and consequently their integrity) influences their pharmacokinetic profile. Thus, the proper arsonoliposome composition should be used according to the intended application.
Zagana
Paraskevi
P
Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, 26500 Rio, Greece.
Haikou
Maria
M
Klepetsanis
Pavlos
P
Giannopoulou
Eleftheria
E
Ioannou
Panayiotis V
PV
Antimisiaris
Sophia G
SG
D000818:Animals; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001151:Arsenic / Q000032:analysis* / Q000097:blood; D018053:Arsenites / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002784:Cholesterol / Q000737:chemistry; D005260:Female; D007274:Injections, Intraperitoneal; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D010168:Palmitates / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D055672:Static Electricity; D013499:Surface Properties; D014018:Tissue Distribution
C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); C526368:2,3-dipalmitoyloxypropylarsonic acid; D000977:Antiparasitic Agents; D018053:Arsenites; D008055:Lipids; D008081:Liposomes; D010168:Palmitates; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D002784:Cholesterol; C010942:1,2-distearoyllecithin; D001151:Arsenic