Echogenic liposomes (ELIP), that can encapsulate\nboth recombinant tissue-type plasminogen activator\n(rt-PA) and microbubbles, are under development to improve\nthe treatment of thrombo-occlusive disease. However,\nthe enzymatic activity, thrombolytic efficacy, and\nstable cavitation activity generated by this agent has yet to\nbe evaluated and compared to another established ultrasound-\nenhanced thrombolytic scheme. A spectrophotometric\nmethod was used to compare the enzymatic activity\nof the rt-PA incorporated into ELIP (t-ELIP) to that of rt-\nPA. An in vitro flow model was employed to measure the\nthrombolytic efficacy and dose of ultraharmonic emissions\nfrom stable cavitation for 120-kHz ultrasound exposure of\nthree treatment schemes: rt-PA, rt-PA and the perfluorocarbon-\nfilled microbubble Definity, and t-ELIP. The enzymatic\nactivity of rt-PA incorporated into t-ELIP was\n28 % that of rt-PA. Thrombolytic efficacy of t-ELIP or rt-\nPA and Definity was equivalent when the dose of t-ELIP\nwas adjusted to produce comparable enzymatic activity.\nSustained bubble activity was nucleated from Definity but\nnot from t-ELIP exposed to 120-kHz ultrasound. These\nresults emphasize the advantages of encapsulating a\nthrombolytic and the importance of incorporating an\ninsoluble gas required to promote sustained, stable\ncavitation activity.
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