Pharmacokinetics of the iron chelator desperrioxamine as affected by liposome encapsulation: potential in treatment of chronic hemosiderosis

Desferrioxamine (DF), the chelator of choice for removal of excess stored iron, is limited by its rapid excretion, metabolic breakdown, and low cell uptake. We have encapsulated DF in unilamellar and multilamellar liposomes, and have compared the short-term pharmacokinetics of nonencapsulated and encapsulated ⁵⁹Fe-labeled DF after intravenous administration. Disappearance of ⁵⁹Fe-DF from the plasma was very rapid in mice receiving multilamellar liposome-encapsulated and nonencapsulated drug, but much slower in mice receiving unilamellar liposomes. Between 1 and 24 hours after injection, nonencapsulated ⁵⁹Fe-DF never exceeded 1–5% of the injected dose (ID) in liver or < 0.7% in spleen; whereas after either multilamellar or unilamellar liposomes, the uptake in liver was 30–35% ID, and in spleen was 1–5% ID. Excretion of ⁵⁹Fe-DF was much slower with liposome encapsulation. These results indicate that liposomes can effectively deliver DF to critical organs of iron storage. Thus this drug delivery system is potentially useful for treatment of iron overload.