Absorption and biodistribution of 111indium-labelled desferrioxamine (111In-DFO) after subcutaneous injection of 111In-DFO liposomes.

In the present study the kinetics of the release of desferrioxamine (DFO) from liposomes (fluid and rigid liposome type) at the subcutaneous (s.c.) injection site was studied. DFO was labelled with 111indium (111In-DFO) and the fate of s.c. administered liposomal 111In-DFO was monitored with a gamma camera. Free 111In-DFO rapidly disappeared from the s.c. injection site [90% of the injected dose (%ID) within 2 h]. After s.c. injection of the fluid liposome type, 20 %ID was released within 4 h and 50 %ID within 24 h. Approximately 25 %ID remained at the injection site 6 days after injection. With the rigid liposome type, no initial release (within 4 h) was observed. The rate of DFO release was similar to the fluid liposome type. Free drug was rapidly cleared from the bloodstream (within 2 h), while low, but detectable blood levels of 111In-DFO were maintained for 6 days after s.c. injection of liposomal drug. This resulted in higher peak levels of 111In-DFO in liver and kidney (4-6 %ID/g) compared with free drug (2-4 %ID/g), which were reached later in time. The present data point to sustained release of DFO from s.c. administered DFO-liposomes as the mechanism behind their enhanced therapeutic effect in murine malaria.