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 PEG 3 500 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.