During the past several years, efforts have been directed toward the design of controlled release prostaglandins and heparin polymers to prevent platelet adhesion and blood clotting at blood polymer interfaces. Currently, prostaglandin releasing polymers are being evaluated in vivo by short-term animal implantation. In this project, the immobilization of heparin and prostaglandins is attempted. We have studied the biological activities of hydroxyl and carboxylic derivatized heparin, synthesized under conditions to specifically prevent intermolecular cross-linking. The well characterized heparin, modified by several chemical processes is being immobilized on surfaces by varying the spacer length used in the immobilization. The AT-III affinity and biological activity, as demonstrated by ACT and APTT tests, of the surface immobilized heparin will be determined. Prostaglandin immobilization using different spacer length is successful, and the stablity and activity of immobilized prostaglandins are being determined by both physical and biological methods. The potent but labile prostacyclin could not be directly immoblized; however, the stable precursor compound is utilized for the immobilization, and a surface reaction is carried to produce active, immobilized prostacyclin.
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