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 antithrombin III to prevent the formation of fibrin clot. In this study, we propose a new method for preparing a heparin-releasing system using a simple solvent casting. The heparin-DOCA conjugate, having an amphiphilic property, was homogeneously mixed with polyurethane in the co-solvent of dioxane, propanol and water. After casting the film, heparin-DOCA was homogeneously dispersed as nanoparticles in a polyurethane film. As the loading amount of heparin-DOCA in the film was increased, nanoparticle size, water uptake, and release rate were increased. Moreover, the percentage of released amount of heparin-DOCA was increased with the increase in the loading amount of heparin-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. The 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 polyurethane films was above 7.5%, the released heparin-DOCA prevented the formation of fibrin clot and the platelet adhesion on the film surface.