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.