Use of Nitric Oxide Donor-Loaded Microbubble Destruction by Ultrasound in Thrombus Treatment
In the presence of a vascular thrombus, the recovery of blood flow and vascular recanalization are very important to prevent tissue damage. An alternative procedure to thrombolysis is required for patients who are unable to receive surgery or thrombolytic drugs due to other physical conditions. Rece...
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MDPI AG
2022-10-01
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author | Ricardo Corro Carlos Franco Urquijo Oscar Aguila Elisa Villa Jesus Santana Amelia Rios Bruno Escalante |
author_facet | Ricardo Corro Carlos Franco Urquijo Oscar Aguila Elisa Villa Jesus Santana Amelia Rios Bruno Escalante |
author_sort | Ricardo Corro |
collection | DOAJ |
description | In the presence of a vascular thrombus, the recovery of blood flow and vascular recanalization are very important to prevent tissue damage. An alternative procedure to thrombolysis is required for patients who are unable to receive surgery or thrombolytic drugs due to other physical conditions. Recently, the performance of thrombolysis combined with microbubbles has become an attractive and effective therapeutic procedure. Indeed, in a recent study, we demonstrated that, upon exposure to ultrasound, liposomes loaded with nitric oxide release agonists conjugated to microbubbles; therefore, there is potential to release the agonist in a controlled manner into specific tissues. This means that the effect of the agonist is potentiated, decreasing interactions with other tissues, and reducing the dose required to induce nitric-oxide-dependent vasodilation. In the present study, we hypothesized that a liposome microbubble delivery system can be used as a hydrophilic agonist carrier for the nitric oxide donor spermine NONOate, to elicit femoral vasodilation and clot degradation. Therefore, we used spermine-NONOate-loaded microbubbles to evaluate the effect of ultrasound-mediated microbubble disruption (UMMD) on thromboembolic femoral artery recanalization. We prepared spermine NONOate-loaded microbubbles and tested their effect on ex vivo preparations, hypothesizing that ultrasound-induced microbubble disruption is associated with the vasorelaxation of aortic rings. Thrombolysis was demonstrated in aorta blood-flow recovery after disruption by spermine NONOate-loaded microbubbles via ultrasound application in the region where the thrombus is located. Our study provides an option for the clinical translation of NO donors to therapeutic applications. |
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language | English |
last_indexed | 2024-03-09T18:49:27Z |
publishDate | 2022-10-01 |
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spelling | doaj.art-eaf21201ce094c9990251303aacafdbb2023-11-24T06:00:28ZengMDPI AGMolecules1420-30492022-10-012721721810.3390/molecules27217218Use of Nitric Oxide Donor-Loaded Microbubble Destruction by Ultrasound in Thrombus TreatmentRicardo Corro0Carlos Franco Urquijo1Oscar Aguila2Elisa Villa3Jesus Santana4Amelia Rios5Bruno Escalante6Cinvestav Monterrey, Centro de Investigación y de Estudios Avanzados del IPN, Apodaca 66600, MexicoCinvestav Monterrey, Centro de Investigación y de Estudios Avanzados del IPN, Apodaca 66600, MexicoCinvestav Monterrey, Centro de Investigación y de Estudios Avanzados del IPN, Apodaca 66600, MexicoCinvestav Monterrey, Centro de Investigación y de Estudios Avanzados del IPN, Apodaca 66600, MexicoCinvestav Monterrey, Centro de Investigación y de Estudios Avanzados del IPN, Apodaca 66600, MexicoCinvestav Monterrey, Centro de Investigación y de Estudios Avanzados del IPN, Apodaca 66600, MexicoCinvestav Monterrey, Centro de Investigación y de Estudios Avanzados del IPN, Apodaca 66600, MexicoIn the presence of a vascular thrombus, the recovery of blood flow and vascular recanalization are very important to prevent tissue damage. An alternative procedure to thrombolysis is required for patients who are unable to receive surgery or thrombolytic drugs due to other physical conditions. Recently, the performance of thrombolysis combined with microbubbles has become an attractive and effective therapeutic procedure. Indeed, in a recent study, we demonstrated that, upon exposure to ultrasound, liposomes loaded with nitric oxide release agonists conjugated to microbubbles; therefore, there is potential to release the agonist in a controlled manner into specific tissues. This means that the effect of the agonist is potentiated, decreasing interactions with other tissues, and reducing the dose required to induce nitric-oxide-dependent vasodilation. In the present study, we hypothesized that a liposome microbubble delivery system can be used as a hydrophilic agonist carrier for the nitric oxide donor spermine NONOate, to elicit femoral vasodilation and clot degradation. Therefore, we used spermine-NONOate-loaded microbubbles to evaluate the effect of ultrasound-mediated microbubble disruption (UMMD) on thromboembolic femoral artery recanalization. We prepared spermine NONOate-loaded microbubbles and tested their effect on ex vivo preparations, hypothesizing that ultrasound-induced microbubble disruption is associated with the vasorelaxation of aortic rings. Thrombolysis was demonstrated in aorta blood-flow recovery after disruption by spermine NONOate-loaded microbubbles via ultrasound application in the region where the thrombus is located. Our study provides an option for the clinical translation of NO donors to therapeutic applications.https://www.mdpi.com/1420-3049/27/21/7218thrombolysisnitric oxide donorsmicrobubbles |
spellingShingle | Ricardo Corro Carlos Franco Urquijo Oscar Aguila Elisa Villa Jesus Santana Amelia Rios Bruno Escalante Use of Nitric Oxide Donor-Loaded Microbubble Destruction by Ultrasound in Thrombus Treatment Molecules thrombolysis nitric oxide donors microbubbles |
title | Use of Nitric Oxide Donor-Loaded Microbubble Destruction by Ultrasound in Thrombus Treatment |
title_full | Use of Nitric Oxide Donor-Loaded Microbubble Destruction by Ultrasound in Thrombus Treatment |
title_fullStr | Use of Nitric Oxide Donor-Loaded Microbubble Destruction by Ultrasound in Thrombus Treatment |
title_full_unstemmed | Use of Nitric Oxide Donor-Loaded Microbubble Destruction by Ultrasound in Thrombus Treatment |
title_short | Use of Nitric Oxide Donor-Loaded Microbubble Destruction by Ultrasound in Thrombus Treatment |
title_sort | use of nitric oxide donor loaded microbubble destruction by ultrasound in thrombus treatment |
topic | thrombolysis nitric oxide donors microbubbles |
url | https://www.mdpi.com/1420-3049/27/21/7218 |
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