Accelerated thrombolysis and reperfusion in a canine model of myocardial infarction by liposomal encapsulation of streptokinase.

Abstract

The aim of thrombolytic therapy for acute myocardial infarction with plasminogen activators such as streptokinase is to lyse the coronary thrombus and reestablish blood flow as quickly as possible so that heart tissue loss is minimized and mortality rates are improved. Streptokinase has been encapsulated in large unilamellar phospholipid vesicles and tested in an animal model of acute myocardial infarction. The time required to restore vessel patency has been reduced more than 50% when compared with findings for free streptokinase. The total dosage of streptokinase required was lower, and smaller remnant thrombi were observed with the encapsulated agent. Results from this initial unoptimized study may have significant implications for further reduction in mortality from heart attacks by therapy with plasminogen activators.

Accelerating thrombolysis with chitosan-coated plasminogen activators encapsulated in poly-(lactide-co-glycolide) (PLGA) nanoparticles

“…Hence, developing new cost-effective formulations or approaches, such as new PA delivery systems, to reduce the risk of side effects of conventional thrombolytic therapy is a worthy goal. For example, the use of liposomal-or PEG-encapsulating SK or t-PA microparticles has been demonstrated significantly to promote fibrinolysis and reduce blood loss in vivo animal [8,10,11] and in vitro models [12][13][14]. Related studies have elucidated the effect hemodynamic forces exerted by fluid on fibrinolysis such as the pressure-or convectiondriven permeation of fluid into clots [12][13][14].…”

“…The clinical benefits of administering PAs for thrombolytic therapy may be markedly improved by developing new methods to promote clot lysis with reduced side effects [7]. In this regard, a drug delivery strategy, such as encapsulating PAs (SK) into liposomes or polymeric microspheres as drug carriers, to increase the therapeutic efficacy of conventional thrombolytic therapy has been demonstrated in in vitro and in vivo animal models [8][9][10][11].…”

The evolution of recombinant thrombolytics: Current status and future directions

“…186 A liposomal encapsulated formulation of streptokinase administered to a canine model of myocardial infarction, reduced the reperfusion time by 50% in comparison to free streptokinase, moreover, the total dose of liposomal streptokinase used was also lower. 187 Platelets play an important role in blood coagulation by formation of the primary platelet plug. The aIIbb3 integrin composed of the glycoproteins IIb/IIIa (GPIIb/IIIa) is the major integrin present on platelets and its activation allows high affinity platelet binding to fibrinogen in the plasma.…”

Drug carriers for vascular drug delivery

“…One example is the early work by Nguyen et al (35), which investigated the thrombolytic efficacy of liposomeencapsulated streptokinase in a canine model of myocardial infarction. The time required to restore vessel patency was reduced by more than 50% with a liposomal enzyme compared with free enzyme.…”