120 kHz pulsed ultrasound enhanced thrombolysis with tissue plasminogen activator-loaded echogenic liposomes

Abstract

Echogenic liposomes (ELIP), phospholipid vesicles filled with gas and fluid, can be manufactured to incorporate the thrombolytic drug tissue plasminogen activator (tPA). Real‐time thrombolysis of blood clots exposed to tPA‐incorporating ELIP (t‐ELIP) was monitored using video microscopy with an inverted optical microscope. Human whole blood clots on silk sutures were exposed to tPA alone (3.15 micrograms/ml), t‐ELIP alone (3.15 micrograms/ml), t‐ELIP and 120 kHz ultrasound (0.18 MPa peak negative pressure, 1.667 kHz pulse repetition frequency, 50% duty cycle), or tPA and ultrasound, for 30 min. The extent of thrombolysis was determined by assessing clot width as a function of time, using a time‐lapse microscopic imaging technique. The average percent change in clot width at 30 min for clots treated with t‐ELIP alone exceeded tPA alone (22.8% vs. 15.6%, respectively). Thrombolytic efficacy was similar for either tPA or t‐ELIP exposed to 120 kHz ultrasound. Thus, the thrombolytic drug could be effectively released by exposure to 120 kHz ultrasound. [This work was supported by The Distinguished Chair for Clinical Research in Emergency Medicine Foundation Award, K02‐NS056253, NIH 1RO1 NS047603, and NIH 1R01 HL074002.]