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

Abstract

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.