The present study compares the efficacy of two formulations of encapsulated
streptokinase to
streptokinase in a rabbit model of
carotid artery thrombosis. Arterial
thrombosis followed the injection of
thrombin mixed with autologous whole blood into a carotid artery of New Zealand white rabbits. Thirty minutes after the confirmation of an occlusive
thrombus, one of four
streptokinase formulations was infused at a dosage of 6000 IU/kg into the jugular vein. Free
streptokinase (FREE SK) was compared to identical dosages of
streptokinase encapsulated in a
liposome (LESK),
streptokinase entrapped in a water-soluble
polymer (
MESK), and free
streptokinase admixed with blank microparticles (FREE SK + BLANK). Carotid arterial blood flow was determined by pulsed Doppler flowmetry to confirm clot formation and reperfusion. Two hours after
drug infusion, the rabbits were killed and the residual
thrombus mass was determined. Compared to FREE SK (74.5 +/- 16.9 min; mean +/- SEM), LESK demonstrated significantly reduced reperfusion times (19.3 +/- 4.6 min) while
MESK exhibited even greater improvement (7.3 +/- 1.6 min). FREE SK + BLANK showed no statistical improvement versus FREE SK. LESK and
MESK also resulted in reduced residual clot mass and greater return of arterial blood flow. These studies suggest that encapsulation of
streptokinase offers a potential method of improved fibrinolytic treatment for patients with clot-based disorders.
MESK performed slightly better than LESK with improved production and storage characteristics.