title: Thrombolytic efficacy and enzymatic activity of rt-PA-loaded echogenic liposomes.
abstract: Echogenic liposomes (ELIP), that can encapsulate both recombinant tissue-type plasminogen activator (rt-PA) and microbubbles, are under development to improve the treatment of thrombo-occlusive disease. However, the enzymatic activity, thrombolytic efficacy, and stable cavitation activity generated by this agent has yet to be evaluated and compared to another established ultrasound-enhanced thrombolytic scheme. A spectrophotometric method was used to compare the enzymatic activity of the rt-PA incorporated into ELIP (t-ELIP) to that of rt-PA. An in vitro flow model was employed to measure the thrombolytic efficacy and dose of ultraharmonic emissions from stable cavitation for 120-kHz ultrasound exposure of three treatment schemes: rt-PA, rt-PA and the perfluorocarbon-filled microbubble Definity(®), and t-ELIP. The enzymatic activity of rt-PA incorporated into t-ELIP was 28 % that of rt-PA. Thrombolytic efficacy of t-ELIP or rt-PA and Definity(®) was equivalent when the dose of t-ELIP was adjusted to produce comparable enzymatic activity. Sustained bubble activity was nucleated from Definity but not from t-ELIP exposed to 120-kHz ultrasound. These results emphasize the advantages of encapsulating a thrombolytic and the importance of incorporating an insoluble gas required to promote sustained, stable cavitation activity.
authors.affiliation: Division of Cardiovascular Health and Disease, Department of Internal Medicine, College of Medicine, Cardiovascular Center 3933, University of Cincinnati, Cincinnati, OH, USA, baderkh@ucmail.uc.edu.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Bader
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bouchoux
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Klegerman
authors.forename: David D
authors.initials: DD
authors.lastname: McPherson
authors.forename: Christy K
authors.initials: CK
authors.lastname: Holland
mesh_terms: D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008081:Liposomes; D045423:Microbubbles; D011994:Recombinant Proteins; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000737:chemistry / Q000494:pharmacology; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D008081:Liposomes; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator
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