Synthesis and anticoagulant function of heparin containing block copolymers on polystyrene microspheres Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/zw12z832w

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  • Contact of blood with the surfaces of synthetic materials is associated with spontaneous protein adsorption, initiating platelet aggregation, the coagulation cascade, and the eventual development of a stable clot. Current therapy to inhibit implant-induced thrombosis is life-long administration of systemic anticoagulants. An alternative to the systemic administration of anticoagulant drugs is to attach a functional anticoagulant agent to the implant surface, thus imparting site-specific activity. Unfractionated heparin (UFH) and an end-aminated form of UFH (HepNH2)were reacted with 2-iminothiolane (2-IT), producing free thiol groups at the sites of internal and terminal amines. Thiolation was quantified using Ellman’s assay and ophthalaldehyde. Thiolated heparin retained anticoagulant activity as shown by the activated partial thromboplastin time (APTT) and anti-Factor Xa (anti-FXa) assays. Surface immobilized, pyridyl disulfide-activated polyethylene oxide chains were used as tethers to attach heparin “end-on” to 1.15 μm polystyrene microspheres. Spectroscopic monitoring of the progress of the reaction indicated that similar amounts of UFH and HepNH2 were attached to the microspheres. The APTT assay showed no anticoagulant activity on heparinized microspheres, due either to the presence of an insufficient amount of immobilized heparin, or to steric constraints inhibiting the formation of a functional heparin-antihrombin complex. However, immobilized heparin did retain anti-FXa activity, with significantly greater activity being recorded at surfaces treated with thiolated HepNH2 than those treated with thiolated UFH.
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