Heeremans J L, Prevost R, Feitsma H, Kluft C, Crommelin D J
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Thromb Haemost. 1998 Jan;79(1):144-9.
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.
在本研究中，在体外闭环流动系统中，将脂质体偶联纤溶酶原的凝块聚集特性与游离（非脂质体）纤溶酶原的特性进行了比较。在将凝块引入封闭系统后，给予双放射性标记的纤溶酶原脂质体，并测量整个凝块上放射性标记的积累。脂质体纤溶酶原在纤维蛋白凝块和全血凝块上的积累均优于游离纤溶酶原。此外，与游离纤溶酶原不同，一旦脂质体纤溶酶原与纤维蛋白结合，就不能用缓冲液冲洗掉。脂质体纤溶酶原能够成功地与过量的游离纤溶酶原竞争。纤溶酶原积累量的平稳水平取决于孵育的纤溶酶原量，并受凝块部分降解的影响。此外，研究表明，为实现最佳凝块积累，需要一个阈值脂质体纤溶酶原表面密度。
