Accelerating effects of ultrasonic thrombolysis with bubble liposomes.
OBJECTIVE
The accelerating effect on thrombolysis by combined use of 500-kHz low-frequency ultrasound (US), recombinant tissue plasminogen activator (rt-PA), and bubble liposomes (BLs) was verified in vitro.


METHODS
A fibrin clot was formed by adding thrombin to bovine plasma. It was enclosed in a pressurized container, the pressure and temperature of which were maintained at 150 mmHg and 37°C, respectively. Ultrasonic conditions were set at a continuous wave, a frequency of 500 kHz, an intensity of 0.7 W/cm(2), and a sonication time of 60 s. We derived the rate of reduction in clot weight from the decreased clot weight and the weight before sonication. We compared the rate of reduction in groups combining physiological saline, rt-PA, BLs, and US.


RESULTS
Only the rt-PA+US+BL group showed a significantly accelerated thrombolytic effect compared with any other group or with any combination of two factors in the 60-s period (0.001 < P < 0.027).


CONCLUSIONS
BLs have great potential to accelerate the thrombolytic effect of rt-PA with low-frequency, 500-kHz, continuous-wave ultrasound.
Medical Engineering Laboratory, Research Center for Medical Science, Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan. taira_z@jikei.ac.jp.
Taira
T
Zenitani
Department of Biopharmaceutics, School of Pharmaceutical Sciences, Teikyo University, Tsukui, Japan.
Ryo
R
Suzuki
Department of Biopharmaceutics, School of Pharmaceutical Sciences, Teikyo University, Tsukui, Japan.
Kazuo
K
Maruyama
Medical Engineering Laboratory, Research Center for Medical Science, Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Hiroshi
H
Furuhata
bubble; liposome; thrombolysis; ultrasound