Development of Control-Release Materials and Its Applications to Cardiovascular Artificial Organs

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The project aimed at development of biomaterials with control release function of anticoagulants and its applications to cardiovascular artificial organs. The matrix polymers selected here was hydrophilic segmented polyurethanes based on poly(ethylene glycol). This segmented polyurethanes prepared here exhibited rubber-like elasticity which satisfies the basic requirements for materials used for cardiovascular artificial organs especially under pulsatile conditions. The hydrophilicity or water-uptake capability was found to be easily controlled by varying the molecular weight of poly(ethylene glycol) as a starting material. The higher the molecular weight is, the higher water-uptake is obtained. The anticoagulants used here were molecularly-designed synthetic drugs named MD-805 and FUT-175. The former was thrombin inhibitor with highly specific and sensitive to thrombin, and the later was synthetic protease inhibitor with wide spectrum including complement inhibition. These synthetic anticoagulants can be easily dissolved into polar aprotic soluents which are good soluents for segmented polyurethanes. The one-step co-casting from a mixed solution of polyurethane and anticoagulant gave homogeneously-dispersed coherent films. The in vitro experiments showed that the systems developed here exhibited superb anticoagulant behavior. The release rate of anticoagulant was monitored, which increased with an increase in water-uptake capability of polymers. The rate and duration of release of anticoagulant was controlled by three variables; 1) materials's variable (hydrophilicity of matrix polymer), 2) formulation's variable (amount of drug loading) and 3) fabrication's variable (coating's thickness). The developed system will provide a new technology of highly anticoagulant materials with controlled release function.