Polymer Therapeutics for Modulating Blood Coagulation and Systemic Iron Sequestration

Abstract: Modern medicine is greatly benefited by the advancement in biomaterials. Synthetic polymers have played critical roles in the success of biomaterial applications and are widely used for drug delivery, drug conjugation, implants, contact lenses, catheters, vascular grafts, cardiovascular stents and dental materials. Focus of our laboratory at the Centre for Blood Research, University of British Columbia (www.cbr.ubc.ca) is tailoring the molecular level interactions of synthetic polymers with biological systems to design novel biomaterials in a translational setting. In this talk, I will discuss the design, synthesis and biological evaluation of two synthetic polymer therapeutics developed in our laboratory. In the first part of the talk, the design, synthesis and evaluation of dendritic polymer based universal heparin reversal agent and polyphosphate inhibitor for the treatment of bleeding and thrombosis will be discussed. The design of new heparin binding groups (HBGs), the presentation of HBGs on the polymer scaffold and the selection of optimized agent based on isothermal titration calorimetry will be explored.  In the second part of the talk, the design of long circulating and long-acting iron chelators for the treatment of systemic iron overload in patients suffering from thalassemia, sickle cell anemia and myelodisplastic syndromes will be detailed.