Rapid and stable accumulation on thrombi of liposomes with attached plasminogen
article
Purpose of the study: characterization of the targeting potential of liposomes with multiple plasminogen molecules on the outside. Background: Liposomes can be loaded with a thrombolytic and on the outside multiple homing devices can be attached for site-specific delivery of the thrombolytic. We tested plasminogen as a candidate for multivalent interaction with the polymer fibrin in thrombi. Methods: An in vitro, closed loop, flow-through model system is used with a total volume of 600 μl and flow rate of 2 ml/min. After introduction of a clot, labelled plg-iiposomes (around 100 pig-molecules /liposomes) are administered and the accumulation of radio-label on the entire clot is measured. Results: plg-iiposomes show increased accumulation over free Pig, both on a fibrin clot and a whole blood clot, in buffer and in plasma. Most importantly, bound free pig can be washed away, while plgiiposomes cannot. Eventually, this results in strong binding of >20% of injected liposomes onto the thrombus. Binding is increased when fibrin is partially proteolysed. Plg-iiposomes are able to compete successfully with an excess of free pig and show a high clot accumulation rate: half maximal binding within 4 circulation times (1.2 min). Conclusions: These in vitro findings indicate that plg-iiposomes may be suitable for rapid and effective in vivo targeting to thrombi. In vivo studies are performed at present with plg-iiposomes loaded with t-PA to verify this.
Topics
TNO Identifier
233633
ISSN
02689499
Source
Fibrinolysis, 10(SUPPL. 3), pp. 83.
Article nr.
Abstract 281
Pages
83
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