Photo-immobilization of dipyridamole (Persantin®) at the surface of polyurethane biomaterials: reduction ofin vitro thrombogenicity

Dipyridamole is a well-known vasodilator and a powerful inhibitor of activation and aggregation of blood platelets. Moreover, dipyridamole is essentially non-toxic. The drug is used extensively in clinical anti-coagulation regimes, for example pre- and post-coronary angioplasty procedures. Recently, we have found that photochemical, covalent coupling of dipyridamole to polyurethane surfaces leads to improved thromboresistancein vitro. This phenomenon is now studied in more detail. Both qualitative and more quantitative biochemical experiments were performed in order to characterize thein vitro blood compatibility of a set of polyurethane surfaces onto which dipyridamole was immobilized. First, scanning electron microscopy was used to examine the morphology of platelets which adhered during incubation with platelet-rich plasma. These experiments showed that immobilization of dipyridamole leads to a clearly decreased number of adherent platelets and to a largely diminished propensity of the surface to activate adherent platelets. Secondly, anin vitro thrombogenicity assay was run. These experiments showed that the thromboresistance increased with increasing surface density of immobilized dipyridamole. A short spacer chain, separating dipyridamole from the polymer surface, was found to improve the thromboresistance further. Such a spacer chain apparently increases the efficacy of the immobilized drug. Collectively, the present results further substantiate the idea that dipyridamole retains its inhibitory activity with respect to activation and aggregation of blood platelets, when the compound is covalently attached to a polymer surface. The possible utility of these findings with respect to the development of an artificial blood vessel prosthesis is discussed briefly.