[Preparation of thrombus-targeted urokinase liposomes and its thrombolytic effect in model rats].
OBJECTIVE
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).


CONCLUSIONS
The targeted UK liposomes displayed good targeted thrombolytic effect.
Wang
Xiang-tao
XT
Department of Pharmaceutics, School of Pharmacy, Peking University, Beijing 100083, China.
Li
Sha
S
Zhang
Xiao-bin
XB
Hou
Xin-pu
XP
D000818:Animals; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D008081:Liposomes; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013678:Technology, Pharmaceutical; D013927:Thrombosis / Q000188:drug therapy*; D016896:Treatment Outcome; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000627:therapeutic use
D004337:Drug Carriers; D005343:Fibrinolytic Agents; D008081:Liposomes; D014568:Urokinase-Type Plasminogen Activator