Thrombolytic efficacy and enzymatic activity of rt-PA-loaded echogenic liposomes.
J Thromb Thrombolysis
; 40(2): 144-55, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-25829338
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Trombose
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Terapia Trombolítica
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Ativador de Plasminogênio Tecidual
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Meios de Contraste
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Microbolhas
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article