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Various plasminogen activators have been routinely used for the treatment of thrombotic diseases. However, these agents possess various problems e.g. short half life and other bleeding complications. To improve the effectiveness as well as to reduce the side effects of these drugs, various modifications have been made. For example, fibrin specific plasminogen activators have been developed. However, these agents also demonstrated various bleeding complications, clinically. Nowadays, so many carrier systems have been explored to improve the activity of these agents. Novel carriers not only improve the effectiveness of these drugs but also reduce the side effects. In the present review, we discuss novel carrier based strategies to improve the delivery of the plasminogen activators to site of thrombus.