We propose to develop a new technique for delivering iron chelators to target organs of iron overload. This technique involves a biological carrier, called a "liposome." The main goal of this project is to enhance the removal of iron deposits in patients suffering from iron overload due to repeated blood transfusions, for example, in Cooley's anemia. We have encapsulated desferrioxamine (DF) in multilamellar liposomes (ML) and unilamellar liposomes (UL). Liposomes were prepared either with dipalmitoyl phosphatidylcholine (Dipalm PC) or galactocerebroside (GC). DF-liposomes are stable; less than 5% of DF leaked out from the liposomes after incubation in mouse plasma for 6 hours. 59Fe-labeled heat damaged erythrocytes (59Fe-DRBC) were administered to nonhypertransfused and hypertransfused mice as models of iron overload. A single injection of ML or UL Dipalm PC-DF or GC-DF liposomes into nonhypertransfused and hypertransfused mice enhanced urinary excretion by 3-to 15-fold. ML-Dipalm PC-DF liposomes significantly reduced the 59Fe content of liver, spleen, small intestine, and bone marrow from nonhypertransfused mice given 59Fe-DRBC's. Liposomes made with Dipalm PC removed from mice given 59Fe-DRBC have more 59Fe-radioactivity than those made with GC. Multilamellar liposomes were also more effective than unilamellar liposomes. These observations suggest that multilamellar Dipalm PC liposomes may have a higher uptake by the Kupffer cells of the liver.
NIH ExPorter
NIH ExPorter