Encapsulated thrombolytic microspheres to prevent reocclusion after thrombolysis and triggered release microspheres to deliver therapeutic drugs

Abstract

Cardiovascular diseases, including acute myocardial infarction, stroke, peripheral arterial diseases, and pulmonary embolism, are the most common and growing cause of morbidity and mortality in the United States. Early reperfusion of occluded blood vessels can be achieved by using thrombolytic therapy. However, thrombolysis is associated with its side effects, including bleeding complications and reocclusion. The hours after treatment for myocardial infarction represent a critical period when the patient is subject to reocclusion and a second coronary event. While rapid release on the order of minutes is desirable initially, an extended half-life of a thrombolytic agent functions better to address reocclusion. The overall goal of this research was the design, synthesis, characterization and testing of microspheres which i) are suitable for extension the half-life of a thrombolytic agent for prevention of reocclusion in vitro, and ii) provide a general controlled release by triggered release mechanism for cardiovascular delivery of therapeutic drugs. The first project of this thesis is to synthesize dextran acetate (DA) with various degrees of substitutions (DA1