Improving thrombolysis with encapsulated plasminogen activators and clinical relevance to myocardial infarction and stroke

Our efforts have focused on investigating the potential benefit of encapsulated thrombolytic agents for treatment of clot-based crises. Liposome encapsulated plasminogen activators (LEPAs) have demonstrated improved thrombolysis in vivo in multiple laboratories. Compared to free agents, LEPAs demonstrate faster reperfusion times, reduced residual clot masses, and more rapid and complete restoration of blood flow. We have encapsulated streptokinase in both liposomes (LESK) and polymer microcapsules (MESK). Both formulations demonstrated reductions in reperfusion times, residual clot mass, and improved return of flow compared to identical dosages of free streptokinase in a thrombosed rabbit carotid, with MESK resulting in comparable or even greater improvements. In addition, marked reductions in bleeding complications and ventricular infarct size have been observed in a canine model of acute myocardial infarction. The mechanism for MESK has recently been explored in our laboratory using multiple microscopic techniques. MESK appears to resist adsorption to the leading edge of the thrombus, a common limitation for the permeation of free plasminogen activators. By avoiding adsorption and penetrating the thrombus, greater spatial distribution of the agent within the clot can be achieved. This data suggests that encapsulation of streptokinase could provide a therapeutic option for treatment of thrombosed arteries.