In Vitro Sonothrombolysis Enhancement by Transiently Stable Microbubbles Produced by a Flow-Focusing Microfluidic Device.

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Title: In Vitro Sonothrombolysis Enhancement by Transiently Stable Microbubbles Produced by a Flow-Focusing Microfluidic Device.
Authors: Dixon, Adam J.1, Rickel, John Marschner Robert1, Shin, Brian D.1, Klibanov, Alexander L.1,2, Hossack, John A.1 jh7fj@virginia.edu
Source: Annals of Biomedical Engineering. Feb2018, Vol. 46 Issue 2, p222-232. 11p.
Subjects: Tissue plasminogen activator, Thrombolytic therapy, Microbubbles, Serum albumin, Thromboembolism
Abstract: Therapeutic approaches that enhance thrombolysis by combining recombinant tissue plasminogen activator (rtPA), ultrasound, and/or microbubbles (MBs) are known as sonothrombolysis techniques. To date, sonothrombolysis approaches have primarily utilized commercially available MB formulations (or derivatives thereof) with diameters in the range 1-4 µm and circulation lifetimes between 5 and 15 min. The present study evaluated the in vitro sonothrombolysis efficacy of large diameter MBs ( d ≥ 10 µm) with much shorter lifetimes that were produced on demand and in close proximity to the blood clot using a flow-focusing microfluidic device. MBs with a N gas core and a non-crosslinked bovine serum albumin shell were produced with diameters between 10 and 20 µm at rates between 50 and 950 × 10 per second. Use of these large MBs resulted in approximately 4.0-8.8 fold increases in thrombolysis rates compared to a clinical rtPA dose and approximately 2.1-4.2 fold increases in thrombolysis rates compared to sonothrombolysis techniques using conventional MBs. The results of this study indicate that the large diameter microbubbles with transient stability are capable of significantly enhanced in vitro sonothrombolysis rates when delivered directly to the clot immediately following production by a flow focusing microfluidic device placed essentially in situ adjacent to the clot. [ABSTRACT FROM AUTHOR]
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  Data: <searchLink fieldCode="DE" term="%22Tissue+plasminogen+activator%22">Tissue plasminogen activator</searchLink><br /><searchLink fieldCode="DE" term="%22Thrombolytic+therapy%22">Thrombolytic therapy</searchLink><br /><searchLink fieldCode="DE" term="%22Microbubbles%22">Microbubbles</searchLink><br /><searchLink fieldCode="DE" term="%22Serum+albumin%22">Serum albumin</searchLink><br /><searchLink fieldCode="DE" term="%22Thromboembolism%22">Thromboembolism</searchLink>
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  Data: Therapeutic approaches that enhance thrombolysis by combining recombinant tissue plasminogen activator (rtPA), ultrasound, and/or microbubbles (MBs) are known as sonothrombolysis techniques. To date, sonothrombolysis approaches have primarily utilized commercially available MB formulations (or derivatives thereof) with diameters in the range 1-4 µm and circulation lifetimes between 5 and 15 min. The present study evaluated the in vitro sonothrombolysis efficacy of large diameter MBs ( d ≥ 10 µm) with much shorter lifetimes that were produced on demand and in close proximity to the blood clot using a flow-focusing microfluidic device. MBs with a N gas core and a non-crosslinked bovine serum albumin shell were produced with diameters between 10 and 20 µm at rates between 50 and 950 × 10 per second. Use of these large MBs resulted in approximately 4.0-8.8 fold increases in thrombolysis rates compared to a clinical rtPA dose and approximately 2.1-4.2 fold increases in thrombolysis rates compared to sonothrombolysis techniques using conventional MBs. The results of this study indicate that the large diameter microbubbles with transient stability are capable of significantly enhanced in vitro sonothrombolysis rates when delivered directly to the clot immediately following production by a flow focusing microfluidic device placed essentially in situ adjacent to the clot. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Annals of Biomedical Engineering is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1007/s10439-017-1965-7
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        Text: English
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      – SubjectFull: Tissue plasminogen activator
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      – SubjectFull: Serum albumin
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              Text: Feb2018
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