HEPARIN ADSORPTION COMPLEXES FOR BLOOD COMPATIBILITY

THE ANTICOAGULANT, HEPARIN, WILL BE DERIVATIZED WITH BIOLOGICALLY COMPATIBLE HYDROPHOBIC MACROMOLECULES TO MAKE THEM WATER INSOLUBLE. THIS DERIVATIZATION WILL OCCUR THROUGH HYDROPHILIC SPACER GROUPS, ALLOWING THE HEPARIN TO EXTEND INTO THE AQUEOUS ENVIRONMENT AND RETAIN ITS BIOACTIVE CONFIGURATION. THESE HEPARIN DERIVATIVES WILL BE SOLVENT-COATED ONTO BIOMEDICAL DEVICES TO PROVIDE LOW-COST, IMMOBILIZED HEPARIN SURFACES APPLICABLE TO ESSENTIALLY ALL TYPES OF POLYMERS USED FOR CATHETERS, TUBING, MEMBRANE OXYGENATORS, ETC. THIS PHASE I PROPOSAL ADDRESSES THE HEPARIN DERIVATIZATION, ADSORPTION STABILITY, TOXICITY, AND BIOLOGICAL EFFECTIVENESS OF THE ADSORPTION COMPLEXES ON SURFACES. LONG-TERM GOALS IN PHASE II INCLUDE SPECIFICALLY TAILORING HIGH MOLECULAR WEIGHT MOLECULES TO BIND TO HEPARIN SO THAT FEWER MOLECULES WOULD NEED TO BE BOUND TO IMMOBILIZE HEPARINTO THE SURFACE. RADIOLABELED EXPERIMENTS WILL BE DONE TO VERIFY THAT NO MODIFIED HEPARIN MOLECULES WILL DESORB IN THE BLOOD ENVIRONMENT. IN VIVO ANIMAL STUDIES WILL BE DONE TO SHOW THE EFFECTIVENESS OF THE IMMOBILIZED HEPARIN IN BOTH ACUTE AND LONG-TERM APPLICATIONS.