CHARACTERIZATION OF IOPROMIDE LIPOSOMES

RATIONALE AND OBJECTIVES. Iopromide-carrying liposomes were prepared a nd were characterized pharmaceutically and biologically. METHODS. The liposomes were prepared by the ethanol evaporation method and were cha racterized by quasi-elastic light scattering (size) and equilibrium di alysis (encapsulation efficiency and stability). Acute and subchronic toxicity was tested in mice and/or rats and cardiovascular tolerance i n rabbits. Pharmacokinetic parameters were determined in rats. Compute d tomography (CT) imaging efficiency was obtained from rat and rabbit studies. RESULTS. The mean diameter was 0.5 +/- 0.1 mum and the encaps ulation efficiency ranged between 30% and 40%. The liposomes were stab le in human and rabbit plasma for approximately 24 hours. The LD50 in mouse and rat was approximately 3 g iodine/kg. In a subchronic toxicit y 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 relevan t computed tomography enhancement of the liver was reached after appro ximately 200 mg iodine/kg in rats and 150 mg iodine/kg in rabbits. CON CLUSIONS. The iopromide-carrying liposomes were well tolerated in anim al studies and seemed to be suitable for the imaging of the liver.