Research Project
3508584
Desferrioxamine (DFO) given intravenously for treatment of Aluminum (Al) intoxication is highly toxic itself. To bypass toxicity we have immobilized DFO into a hollow fiber device for the extracorporeal removal of Al from blood. Such a device (similar to a hemodialysis cartridge) is a novel approach to detoxification with unique advantages: (1) The immobilized chelator does not enter the blood, toxicity is minimized. (2) The device is highly efficient due to large contact area with high concentrations of chelator and specific toward a given metal according to chelator used. (3) Blood compatibility of hollow fibers assures safety of application. In Phase I we have prepared and tested 4 DFO conjugates and 2 commercial resins immobilized into hollow fiber cartridges. When tested with recirculating Al solutions and patient's blood the degree of Al removal was of clinical significance. For Phase II, 3 DFO-conjugates were selected to be immobilized into chelator device and tested for Al uptake using recirculating saline with (a) high Al level (25 mg/L), (b) low Al level (100 mcg/L), and low Al level kept constant during the experiment with Al delivery in the reservoir from a pump. Blood from dialysis patients will be recirculated through chelator devices to examine if the amount of ultrafiltrable Al increases during the experiment, at the expense of the protein bound fraction. Steps in manufacturing will be streamlined. The best performing chelator device will be developed as a prototype and will be tested in animals for safety of in vivo application.
