Polycationic calix[8]arene receptors grafted onto polymeric matrix: smart material for heparin neutralization

Heparin is widely prescribed as an anticoagulant medicine and is beneficial to millions of patients. However, the use of heparin in open-heart surgery, where it enables a continuous flow of blood throughout the process, is still problematic. Its anticlotting properties are crucial for a successful operation, but after surgery the patient's blood needs to return normal and acquire its former ability to coagulate. If this process fails, the outcome may prove fatal. Currently, protamine sulfate is used to neutralize heparin after open-heart surgery. However, protamine itself causes allergic reactions and other side effects and is sometimes fatal. For this reason, the finding of new heparin antagonists or much safer methods for heparin removal from blood is currently of great interest. Recently we have reported on the synthesis of calix[8]arene polycations that have shown an exceptional neutralization power towards heparin both in physiological solution and in blood. In this work, we have studied the grafting of these calix[8]arene derivatives onto a polymeric matrix with the aim to obtain a new polymeric material appropriate for the design and realization of filters or membranes able to effectively remove heparin from blood. In this way, also the side effects connected to systemic administration of heparin antagonists are avoided. Besides the synthesis, preliminary results on the neutralization capacity towards heparin, both in physiological solution and in blood, are reported.