(527f) Tissue Plasminogen Activator Carrying Worm Micelles as Prophylactic Fibrinolytic Agents

Synthetic polymer carrier, worm micelles, could improve the therapeutic potential of blood clot dissolving tissue plasminogen activator (tPA). Tissue plasminogen activator (tPA) is a clot-dissolving therapeutic protein, which is used in patients having a heart attack or stroke. Although tPA has saved numerous lives in clinical use, the short circulation time in vivo and the severe side effect as neurotoxicity has been pointed out as problems which should be solved. To overcome these shortcomings, worm micelles were coupled with tPA, because worm micelles are known to have long-circulation time due to its flexible nature and inert polyethylene oxide brushes preventing rapid phagocytosis. While maintaining fibrinolytic activity, tissue plasminogen activator could be attached to worm micelles and worm micelles also maintained their flexibility. The selective binding of flexible tPA-worm micelles to fibrinogen was observed using total internal reflectance fluorescence microscope (TIRF). In a model of venous thrombosis induced by intravenously injected fibrin micro emboli aggregating in pulmonary vasculature, worm micelles were interacting severely with pulmonary micro emboli. Combining advantages of therapeutic protein and long-circulating carrier system, this worm micelle based tPA delivery permits prophylactic fibrinolysis.