title: The preparation of a new self-made microbubble-loading urokinase and its thrombolysis combined with low-frequency ultrasound in vitro.
abstract: 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 × 10(8)/mL, ∼3.13 μm, 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.
authors.affiliation: Department of Pathology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Ren
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Wang
authors.forename: Bo-Bin
authors.initials: BB
authors.lastname: Jing
authors.forename: Ying-Xue
authors.initials: YX
authors.lastname: Li
authors.forename: Yi-Ran
authors.initials: YR
authors.lastname: Liao
authors.forename: Xiao-Ning
authors.initials: XN
authors.lastname: Kang
authors.forename: Wei-Jin
authors.initials: WJ
authors.lastname: Zang
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
mesh_terms: D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000737:chemistry*; D005612:Freeze Drying; D066298:In Vitro Techniques; D045423:Microbubbles; D015912:Thrombolytic Therapy / Q000379:methods*; D014464:Ultrasonic Therapy / Q000379:methods*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D005343:Fibrinolytic Agents; D014568:Urokinase-Type Plasminogen Activator