A novel formulation for controlled release of heparin-DOCA conjugate dispersed as nanoparticles in polyurethane film

Heparin is a potent anticoagulant agent that interacts strongly with antith rombin III to prevent the formation of fibrin clot. In this study, we propo se a new method for preparing a heparin-releasing system using a simple sol vent casting. The heparin-DOCA conjugate, having an amphiphilic property, w as homogeneously mixed with polyurethane in the co-solvent of dioxane, prop anol and water. After casting the him, heparin-DOCA was homogeneously dispe rsed as nanoparticles in a polyurethane film. As the loading amount of hepa rin-DOCA in the film was increased, nanoparticle size, water uptake, and re lease rate were increased. Moreover, the percentage of released amount of h eparin-DOCA was increased with the increase in the loading amount of hepari n-DOCA. This was because the size of heparin-DOCA particles increases with the increase in the loading amount of heparin-DOCA, thereby decreasing the distance between particles and the total diffusion length to the surface. T he release rate of heparin-DOCA can be controlled by the amount of the drug being loaded and the film thickness. When the heparin-DOCA loaded on the p olyurethane films was above 7.5%, the released heparin-DOCA prevented the f ormation of fibrin clot and the platelet adhesion on the film surface. (C) 2000 Elsevier Science Ltd. All rights reserved.