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The Preparation of a New Self-Made Microbubble-Loading Urokinase and Its Thrombolysis Combined with Low-Frequency UltrasoundIn Vitro

Authors
Journal
Ultrasound in Medicine & Biology
0301-5629
Publisher
Elsevier
Publication Date
Volume
37
Issue
11
Identifiers
DOI: 10.1016/j.ultrasmedbio.2011.06.018
Keywords
  • Microbubbles
  • Urokinase
  • Thrombolysis
  • Low-Frequency Ultrasound
  • Drug Local Deliver
Disciplines
  • Chemistry
  • Medicine

Abstract

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.

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