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Thromb Haemost 1997; 77(06): 1174-1178
DOI: 10.1055/s-0038-1656133
Fibrinolysis
Schattauer GmbH Stuttgart

Streptokinase Entrapment in Interdigitation-Fusion Liposomes Improves Thrombolysis in an Experimental Rabbit Model

W R Perkins
1   The Liposome Company, Inc., 1 Research Way, Princeton, NJ, USA
,
D E Vaughan
2   Cardioiogy Division, Brigham and Womens Hospital and West Roxbury VAMC, Boston, MA, USA
,
S R Plavin
2   Cardioiogy Division, Brigham and Womens Hospital and West Roxbury VAMC, Boston, MA, USA
,
W L Daley
2   Cardioiogy Division, Brigham and Womens Hospital and West Roxbury VAMC, Boston, MA, USA
,
J Rauch
3   The Montreal General Hospital Research Institute, McGill University, Montreal, Quebec, Canada
,
L Lee
1   The Liposome Company, Inc., 1 Research Way, Princeton, NJ, USA
,
A S Janoff
1   The Liposome Company, Inc., 1 Research Way, Princeton, NJ, USA
› Author Affiliations
Further Information

Publication History

Received 14 May 1996

Accepted after revision 10 March 1997

Publication Date:
26 July 2018 (online)

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Summary

The successful design of new thrombolytic agents depends on providing these agents with increased clot selectivity. As recently demonstrated (10), entrapment of tissue plasminogen activator into liposomes apparently provided the selective targeting needed to improve the efficacy of this fibrinolytic agent. To test whether liposomal entrapment would benefit streptokinase, a fibrinolytic agent with a different mode of action and inactivation, we compared liposomal streptokinase with free streptokinase in an experimental rabbit model of thrombolysis.

First we adapted a new method to produce liposomes of high entrapment efficiency, termed interdigitation-fusion (IF) liposomes, for the encapsulation of streptokinase. This system was then tested in an in vivo rabbit model of thrombolysis where animals with established clots were infused with either free streptokinase (40,000 U/kg), liposomally entrapped streptokinase, free streptokinase + empty liposomes, or the corresponding amount of empty liposomes or saline. Significant differences (p <0.05) in the percent clot lysis were observed between saline control (22.4 ± 3.3%; mean ± S.E.), free streptokinase (36.3 ± 3.4%), and liposomal streptokinase (47.4 ± 1.4%). Importantly, animals treated with empty liposomes experienced a level of thrombolysis (32.4 ± 2.8%) not different to that produced by free streptokinase or empty liposomes plus free streptokinase (38.0 ± 2.0%). We believe the effect of liposomes alone is due to a transient redistribution or margination of circulating platelets.

When tested in rabbits immunized against streptokinase, liposomal (33.8 ± 1.5%) but not free streptokinase (29.3 ± 2.1%) showed significant thrombolytic activity compared to saline (22.4 ± 3.3%) (p <0.05). The thrombolytic activity was comparable to free streptokinase in nonimmunized rabbits. This suggests liposomal streptokinase would have better thrombolytic activity than streptokinase alone and still provide to those patients possessing high levels of anti-streptokinase antibodies (5% of the population) the equivalent degree of therapy expected from free streptokinase.

 

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