We propose to study and develop the red blood cell ghost (RBCG) as a delivery system for iron chelators to reticuloendothelial (RE) iron stores. We have entrapped the iron chelator desferrioxamine (DF) into resealed human and rat red blood cell ghosts, and in preliminary experiments, have shown several fold enhancement of iron excretion in rats given DF in RBCGs compared with intravenous DF alone. RBCG's are taken up by RE cells of the spleen and liver, the primary and major sites of iron deposition in thalassemia and other iron-loading anemias. Using the RBCG as a Trojan Horse for delivery of DF into RE cells, we will measure the rates of iron loss in normal, iron-loaded and hypertransfused rats, and compare them to the rates after DF is given through other routes. We will measure new iron excretion by radioisotopic and chemical methods. Iron losses in urine and feces will be measured chemically as well as the decrement in hepatic and splenic non-heme iron. In radioisotopic studies, losses in excreta as well as whole body retention of radioiron will be measured in rats with uniformly labeled iron stores. Other iron chelators will be similarly studied. We shall study the distribution and fate of chelators entrapped in RBCGs. We are seeking to develop this technique as a potential improvement of existing methods to treat the iron overload of thalassemia and related conditions. The approach should also provide useful information on the availability for chelation of storage iron from different anatomic sites.