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English Abstract
Journal Article
Research Support, Non-U.S. Gov't
[Preparation of thrombus-targeted urokinase liposomes and its thrombolytic effect in model rats].
Yao Xue Xue Bao = Acta Pharmaceutica Sinica 2003 March
AIM: To prepare thrombus-targeted urokinase liposomes and observe its improved thrombolytic efficacy on thrombus model rats.
METHODS: The ligand H-Arg-Gly-Asp-Ser-OH (RGDS) which has specific affinity to thrombus was synthesized by liquid phase method and anchored on the surface of liposomes by incorporating its conjugate with DSPE-PEG3,500-COOH into liposomal lipid bilayers, thus thrombus-targeted liposomes were produced. Urokinase (UK) liposomes were prepared at room temperature through method modification using hydrogenated soy phosphatidylcholine (HSPC); the in vivo thrombolysis of the obtained thrombus-targeted UK liposomes and its comparison with TBS (Tris-HCl buffered solution) control, free UK and UK liposomes were assessed on common carotid artery model rats.
RESULTS: The obtained liposomes were characteristic of high UK entrapment efficiency, small mean diameter and good storage stability. At the same dose (60,000 U.kg-1), compared to the wet thrombi weights of TBS control group, those of free UK group and UK liposome group showed no statistical difference, while those of targeted UK liposomes group were significantly decreased (P < 0.001); when evaluated in term of dry thrombi weights the result was slightly different. Compared to UK liposomes of the same dose, the targeted UK liposomes showed significantly improved thrombolytic efficacy (P < 0.01 in wet weights decrease and P < 0.05 in dry weights decrease respectively).
CONCLUSION: The targeted UK liposomes displayed good targeted thrombolytic effect.
METHODS: The ligand H-Arg-Gly-Asp-Ser-OH (RGDS) which has specific affinity to thrombus was synthesized by liquid phase method and anchored on the surface of liposomes by incorporating its conjugate with DSPE-PEG3,500-COOH into liposomal lipid bilayers, thus thrombus-targeted liposomes were produced. Urokinase (UK) liposomes were prepared at room temperature through method modification using hydrogenated soy phosphatidylcholine (HSPC); the in vivo thrombolysis of the obtained thrombus-targeted UK liposomes and its comparison with TBS (Tris-HCl buffered solution) control, free UK and UK liposomes were assessed on common carotid artery model rats.
RESULTS: The obtained liposomes were characteristic of high UK entrapment efficiency, small mean diameter and good storage stability. At the same dose (60,000 U.kg-1), compared to the wet thrombi weights of TBS control group, those of free UK group and UK liposome group showed no statistical difference, while those of targeted UK liposomes group were significantly decreased (P < 0.001); when evaluated in term of dry thrombi weights the result was slightly different. Compared to UK liposomes of the same dose, the targeted UK liposomes showed significantly improved thrombolytic efficacy (P < 0.01 in wet weights decrease and P < 0.05 in dry weights decrease respectively).
CONCLUSION: The targeted UK liposomes displayed good targeted thrombolytic effect.
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