THE PREPARATION OF A NEW SELF-MADE MICROBUBBLE-LOADING UROKINASE AND ITS THROMBOLYSIS COMBINED WITH LOW-FREQUENCY ULTRASOUND IN VITRO

Urokinase (uPA) is used widely for thrombosis therapy in the clinic. However, ways to minimize its adverse effect of hemorrhage are still being studied. As a new technique for the local delivery of genes and drugs, ultrasound (US) contrast agents, microbubbles (MBs), have been mentioned. The purpose of this study is to explore a more efficacious and safer thrombolytic method by preparing three groups of self-made microbubble-loading uPA (uPA-MBs) (1 uPA-MBs, 5 uPA-MBs and 10 uPA-MBs) using freeze-drying methods and measuring their thrombolysis when combined in vitro with low-frequency US. The results showed the mean concentration, mean diameter, pH value and encapsulation efficiency of uPA of the three groups of uPA-MBs were approximately 2.08-2.82 x 10(8) /mL, similar to 3.13 mu m, 6.89-6.99 and from (78.08% +/- 0.57%) to (57.23% +/- 0.94%), respectively. Under US exposure, the loaded uPA demonstrated bioactivity by agarose fibrin plate and in vitro thrombolysis of the three uPA-MBs also showed higher effects than in the group of those who received uPA-MBs alone, the control group or the US group. In conclusion, the physiochemical properties of these self-made uPA-MBs are suitable for intravenous administration but 1 uPA-MB and 5 uPA-MBs are better than 10 uPA-MBs. uPA-MBs combined with US can decrease the in vitro dosage of uPA for thrombolysis. (E-mail: wangbing@mail.xjtu.edu.cn) (C) 2011 World Federation for Ultrasound in Medicine & Biology.