PDF herunterladen
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
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 24. April 1997

Accepted after revision 12. August 1997

Publikationsdatum:
08. Dezember 2017 (online)

Auch verfügbar auf
    Lizenzen und Reprints

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


 

  • References

  • 1 Crommelin DJA, Schreier H. Liposomes. In: Colloidal drug delivery systems. Kreuter J. ed. New York: Marcel Dekker Inc; 1994. pp 73-90.
    Suche in Google Scholar
  • 2 Crommelin DJA, Scherphof G, Storm G. Active targeting with particulate carrier systems in the blood compartment. Adv Drug Del Rev 1995; 17: 49-60.
    CrossrefPubMedSuche in Google Scholar
  • 3 Heeremans JLM, Kraaijenga JJ, Los P, Kluft C, Crommelin DJA. Development of a procedure for coupling the homing device Glu-plasminogen to liposomes. Biochim Biophys Acta 1992; 1117: 258-64.
    CrossrefPubMedSuche in Google Scholar
  • 4 Heeremans JLM, Crommelin DJA, Kluft C. Pharmaceutical composition for site-specific release of a clot-dissolving protein. Internat. Patent Appl. No. WO 94 / 07537, 1994.
    PubMed
  • 5 Heeremans JLM, Prevost R, Bekkers MEA, Los P, Emeis JJ, Kluft C, Crommelin DJA. Thrombolytic treatment with tissue-type plasminogen activator (t-PA) containing liposomes in rabbits: a comparison with free t-PA. Thromb Haemost 1995; 73: 488-94.
    Thieme ConnectPubMedSuche in Google Scholar
  • 6 Heeremans JLM, Los P, Prevost R, Crommelin DJA, Kluft C. Fibrin binding of Glu-plasminogen coated liposomes in vitro. Thromb Haemost 1996; 75: 134-9.
    Thieme ConnectPubMedSuche in Google Scholar
  • 7 Martin FJ, Papahadjopoulos D. Irreversible coupling of immunoglobulin fragments to preformed vesicles. An improved method for liposome targeting. J Biol Chem 1982; 257: 286-8.
    PubMedSuche in Google Scholar
  • 8 Ruyven-Vermeer IAM van, Nieuwenhuizen W. Purification of rat fibrinogen and its constituent chains. Biochem J 1978; 169: 653-8.
    CrossrefPubMedSuche in Google Scholar
  • 9 Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 1965; 13: 238-52.
    CrossrefPubMedSuche in Google Scholar
  • 10 Heeremans JLM, Prevost R, Bischot L, Los P, Kluft C, Crommelin DJA. Interference of ε-amino-caproic acid with [N-succinimidyl S-acethylace-tate derived] thiol introduction into Glu-plasminogen. Fibrinolysis 1994; 8 (Suppl. 02) 138-41.
    PubMedSuche in Google Scholar
  • 11 Fraker PJ, Speck JC. Protein and cell membrane iodinations with a sparingly soluble choloroamide, 1,3,4,6,-tetrachloro-3a, 6a-diphenylglycoluril. Biochem Biophys Res Commun 1978; 80: 849-57.
    CrossrefPubMedSuche in Google Scholar
  • 12 Duncan RJS, Weston PD, Wrigglesworth R. A new reagent which may be used to introduce sulfhydryl groups into proteins, and its use in the preparation of conjugates for immunoassay. Anal Biochem 1983; 132: 68-73.
    CrossrefPubMedSuche in Google Scholar
  • 13 Sakharov DV, Rijken DC. Superficial accumulation of plasminogen during plasma clot lysis. Circulation 1995; 92: 1883-90.
    CrossrefPubMedSuche in Google Scholar
  • 14 Thorsen S. The mechanism of plasminogen activation and the variability of the fibrin effector during tissue-type plasminogen activator-mediated fibrinolysis. Ann N Y Acad Sci 1992; 667: 52-63.
    CrossrefPubMedSuche in Google Scholar
  • 15 Bell GI. Physical chemical aspects of cell surface events in cellular regulation. Delisi C, Blumenthal R. eds. North-Holland: Elsevier NY; 1979
    Suche in Google Scholar
  • 16 Ho RJY, Rouse BT, Huang L. Target-sensitive immunoliposomes: preparation and characterization. Biochemistry 1986; 25: 5500-6.
    CrossrefPubMedSuche in Google Scholar
  • 17 Ho RJY, Rouse BT, Huang L. Target-sensitive immunoliposomes as an efficient drug carrier for antiviral activity. J Biol Chem 1987; 262: 13973-8.
    PubMedSuche in Google Scholar
  • 18 Wasser MNJM, Nieuwenhuizen W, Pauwels EKJ. Scintigraphic detection of thrombi using a Tc-99m labelled antifibrin monoclonal antibody: experiments in vitro and in animals. Proc symposium Clinical use of monoclonal antibodies. Amsterdam: 1988: 122.
    Suche in Google Scholar