Thromb Haemost 1998; 79(01): 144-149
DOI: 10.1055/s-0037-1614234
Review Article
Schattauer GmbH

Clot Accumulation Characteristics of Plasminogen-bearing Liposomes in a Flow-system

J. L. M. Heeremans
1   The Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences*, Utrecht University, Utrecht, The Netherlands
3   Gaubius Laboratory, TNO-PG, Leiden, The Netherlands
,
R. Prevost
1   The Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences*, Utrecht University, Utrecht, The Netherlands
3   Gaubius Laboratory, TNO-PG, Leiden, The Netherlands
,
H. Feitsma
2   Academic Hospital Leiden, Leiden, The Netherlands
,
C. Kluft
3   Gaubius Laboratory, TNO-PG, Leiden, The Netherlands
,
D. J. A. Crommelin
1   The Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences*, Utrecht University, Utrecht, The Netherlands
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Publikationsverlauf

Received 24. April 1997

Accepted after revision 12. August 1997

Publikationsdatum:
08. Dezember 2017 (online)

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Summary

In this study, the clot accumulation properties of liposome-coupled plasminogen were compared to those of free (non-liposomal) plasminogen in an in vitro, closed-loop, flow-system. After introduction of a clot into the closed system, double-radiolabelled plasminogen-liposomes were administered and the accumulation of radiolabel on the entire clot was measured.

Liposomal plasminogen showed improved accumulation over free plasminogen, on both a fibrin clot and a whole blood clot. Moreover, once liposomal plasminogen was fibrin associated, it could not be washed away with buffer, in contrast to free plasminogen. Liposomal plasminogen was able to compete successfully with an excess of free plasminogen. The plateau levels for the accumulated amount of plasminogen depended on the incubated amount of plasminogen and were influenced by partial degradation of the clot. Furthermore, it was shown that a threshold liposomal plasminogen surface-density was needed for optimum clot accumulation.

*Participant in the Groningen Utrecht Institute for Drug Exploration, GUIDE