The ultrasound contrast imaging properties of lipid microbubbles loaded with urokinase in dog livers and their thrombolytic effects when combined with low-frequency ultrasound in vitro
- 276 Downloads
A new microbubble loaded with urokinase (uPA-MB) was explored in a previous study. However, its zeta potential and ultrasound contrast imaging properties and its thrombolytic effects when combined with low-frequency ultrasound (LFUS) were unclear. The zeta potential and ultrasound contrast imaging property of 5 uPA-MBs loading with 50,000 IU uPA was respectively detected using a Malvern laser particle analyzer and a Logiq 9 digital premium ultrasound system. Its ultrasound contrast imaging property was performed on the livers of two healthy dogs to compare with SonoVue. And the clot mass loss rate, D-dimer concentration and surface morphology of the clot residues were measured to evaluate the thrombolytic effect after treatment with three doses of 5 uPA-MBs combined with LFUS in vitro. The zeta potential of 5 uPA-MBs (−27.0 ± 2.40 mV) was higher than that of normal microbubbles (−36.95 ± 1.77 mV). Contrast-enhanced imaging of the hepatic vessels using 5 uPA-MBs was similar to SonoVue, while the imaging duration of 5 uPA-MBs (10 min) was longer than SonoVue (6 min). The thrombolytic effect of three doses of uPA-MBs combined with LFUS was significantly better than that of the control group and showed dose dependence. The 5 uPA-MBs have a negative charge on their surface and good echogenicity as ultrasound contrast agents. The 5 uPA-MBs combined with LFUS can promote thrombolysis in a dose-dependent manner.
KeywordsMicrobubble Ultrasound contrast imaging Urokinase Thrombolysis
The authors would like to thank Hua-Sheng Liu, Shao-Li Cheng, and Jiang-Wei Liang for help in the experiment. The present study was supported by the Scientific Technology Planning Foundation of Shaanxi Province (No. 2010K12-01), the National 863 Plan (No. 2010AA022907), the National Natural Science Foundation (General Program, No. 30872410), Province Ministry Graveness Engineering Program (Nos. 2009ZDKG-20, 2008ZDKG-60, 2007ZDKG-290) and Xi’an Jiaotong University Project (Nos. 2009xjtujc14 and 2009xjtujc26).
Conflict of interest
All authors declare that there are no financial or personal relationships that might lead to conflict of interest.