Characterization of iopromide liposomes.
OBJECTIVE
Iopromide-carrying liposomes were prepared and were characterized pharmaceutically and biologically.


METHODS
The liposomes were prepared by the ethanol evaporation method and were characterized by quasi-elastic light scattering (size) and equilibrium dialysis (encapsulation efficiency and stability). Acute and subchronic toxicity was tested in mice and/or rats and cardiovascular tolerance in rabbits. Pharmacokinetic parameters were determined in rats. Computed tomography (CT) imaging efficiency was obtained from rat and rabbit studies.


RESULTS
The mean diameter was 0.5 +/- 0.1 micron and the encapsulation efficiency ranged between 30% and 40%. The liposomes were stable in human and rabbit plasma for approximately 24 hours. The LD50 in mouse and rat was approximately 3 g iodine/kg. In a subchronic toxicity study in rats with six doses of 1 g iodine/kg given every three days, no adverse effects were observed. The pharmacokinetics in rats were dose-dependent. Increasing the dose resulted in lower total clearance, and longer terminal half-life. Elimination of iodine was complete and the main route of excretion was via the kidneys. A clinically relevant computed tomography enhancement of the liver was reached after approximately 200 mg iodine/kg in rats and 150 mg iodine/kg in rabbits.


CONCLUSIONS
The iopromide-carrying liposomes were well tolerated in animal studies and seemed to be suitable for the imaging of the liver.
Krause
W
W
Schering AG, Berlin, Germany.
Leike
J
J
Sachse
A
A
Schuhmann-Giampieri
G
G
D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007472:Iohexol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D008081:Liposomes; D008099:Liver / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014057:Tomography, X-Ray Computed
D003287:Contrast Media; D008081:Liposomes; D007472:Iohexol; C038192:iopromide