Acute myocardial infarction accounts for approximately 700,000 hospitalizations annually. One therapeutic approach to this problem is the application of thrombolytic agents, such as streptokinase, to produce reperfusion of the ischemic myocardial tissue. Unfortunately, recent experimental evidence seems to indicate that irreversible cellular damage occurs when ischemic myocardium is reperfused with oxygenated blood. One possible mechanism of tissue damage is through the formation of hydroxyl or other oxyradical species during reperfusion. We propose to encapsulate antioxidant enzymes such as superoxide dismutase in liposomes to increase the circulating half-life and concentration of these enzymes. Liposomal antioxidant enzyme formulations will be prepared and characterized during the first segment of this work. Pharmacokinetics in rats will then be performed with selected enzyme-vesicle formulations in order to demonstrate increased and prolonged blood, and possibly tissue, levels of protective enzyme activities. If successful, this technology could lead to a product which would be useful in the management of acute myocardial infarction.
