IMPROVED BINDING OF ANTITHROMBOGENIC AGENTS TO POLYMERS

WE WILL DEVELOP AND EVALUATE POLYMER COATINGS CONTAINING ANTICOAGULANT DRUGS. THESE POLYMERS, WHEN APPLIED TO THE SURFACE OF A PROSTHESIS THAT COMES IN CONTACT WITH BLOOD, RENDERS THE DEVICE NONTHROMBOGENIC. THUS FREQUENTLY ENCOUNTERED CLINICAL COMPLICATIONS RELATED TO THROMBUS FORMATION ARE MINIMIZED AND MORBIDITY IS DECREASED. THIS PROJECT FOCUSES ON IMPROVING THE BIOCOMPATIBILITY OF TWO SPECIFIC DEVICES, I.E., HEMOFILTERS AND EXTRACORPOREAL MEMBRANE OXYGENATORS, BUT THE PROMISE TO BE USEFUL IN OTHER PROSTHESES IN WHICH THROMBOGENESIS IS A MAJOR PROBLEM, FOR EXAMPLE, IN SMALL-DIAMETER VASCULAR GRAFTS AND IN THE TOTAL ARTIFICIAL HEART. EXPERIMENTALLY WE WILL REDUCE THROMBOGENICITY BY APPLYING POLYMER COATINGS CONTAINING SLOW-RELEASE FORMULATIONS OF ANTITHROMBOGENIC DRUGS TO THE SURFACE OF EXTRACORPOREAL DEVICES. SPECIFICALLY, WE INTEND TO TARGET THE PLATELET INHIBITORY EFFECTS OF ILOPROST (A CHEMICALLY STABLE PROSTACYCLIN ANALOG NOW IN CLINICAL TRIALS), AND HEPARIN (A NATURALLY OCCURRING ANTICOAGULANT) BY ENTRAPPING THESE DRUGS IN SURFACE COATINGS APPLIED TO EXTRACORPOREAL DEVICES. THE PHARMACOLOGICAL AGENTS ARE NOT IRREVERSIBLY BOUND TO THE PROSTHESIS, AND AFTER EXPOSURE TO BLOOD THE DRUGS ARE SLOWLY RELEASED PROVIDING A LOCAL ENVIRONMENT OF HIGH DRUG CONCENTRAION AT THE SURFACE OF THE PROSTHESIS. THIS PROMOTES LOCALIZED INHIBITION OF PLATELET ACTIVATION AND INHIBITION OF FIBRIN FORMATION.