Successful photoimmobilization of active, stable heparinase on surface modified polymeric microspheres ill yield an important technology for removal from blood of heparin required during hemodialysis. cardiopulmonary bypass and vascular surgery. The availability of this technology for heparin removal would eliminate the requirement for neutralization of heparin by the addition of a compound which has deleterious side effects (protamine). The improvements predicted from the successful execution of this project will be the combined advantages of rigid polymeric support (polystyrene), modified by photoimmobilized hydrophilic polymer spacers and reactive functions to achieve highly efficient heparinase coupling. The use of photochemistry for the proposed surface modification and immobilization will eliminate the requirement for the toxic activating chemistry which is currently used for enzyme immobilization. Development of these photoimmobilization chemistries has more universal significance for enzyme deficiency diseases. This technology can be adapted to a variety of device formats for enzyme replacement therapies which require covalent coupling and stabilization of enzymes for long term in vivo placement. The Phase I project is designed to demonstrate feasibility for photoimmobilization of heparinase to modified microspheres, and is expected to provide the basis for continuation in the development of highly active, stabilized and immune-masked therapeutic enzymes immobilized firmly to blood-compatible biomaterial surfaces.
The proposed technology has high commercial value. Successful completion of this research effort will provide significant technical advancement for immobilization of highly active, stable enzymes for extracorporeal removal of toxic molecules, such as heparin. The proposed surface modification for enzyme immobilization could be easily adapted to other devices for enzyme replacement therapies for inborn errors in metabolism.
