Enhancement of iron chelation by desferrioxamine entrapped in red blood cell ghosts

Abstract

We have exploited the physiologic mechanism for removal of red cells from the circulation to target the iron chelator desferrioxamine to reticuloendothelial iron stores. Compared with free desferrioxamine injected intravenously, the same dose of desferrioxamine entrapped in resealed red blood cell ghosts resulted in a fourfold to fivefold increase in excretion of radioiron in rats with a selective 59Fe radiolabel of reticuleondothelial iron stores. Desferrioxamine in red cell ghosts did not enhance excretion in rats with selective radiolabeling of parenchymal iron stores. In rats with uniformly radiolabeled iron stores, desferrioxamine in red cell ghosts produced an eightfold to ninefold greater loss of iron in the urine than free desferrioxamine intravenously or by slow subcutaneous infusion. Desferrioxamine in red cell ghosts resulted in significantly greater fecal excretion of iron than intravenous desferrioxamine, but desferrioxamine in red cell ghosts and subcutaneous desferrioxamine infusion resulted in similar fecal iron excretion. Clinical application of the red cell ghost method for administration of desferrioxamine and other iron chelators may be useful for improvement of iron chelation efficiency.