Abstract:One of the great advancements in the applications of piezoelectric materials is the application for therapeutic medical ultrasound for sonothrombolysis. Sonothrombolysis is a promising ultrasound based technique to treat blood clots compared to conventional thrombolytic treatments or mechanical thrombectomy. Recent clinical trials using transcranial Doppler ultrasound, microbubble mediated sonothrombolysis, and catheter directed sonothrombolysis have shown promise. However, these conventional sonothrombolysis … Show more
“…Sonothrombolysis has been particularly effective at treating unretracted blood clots and improving tPA treatment by incorporating ultrasound contrast agents such as microbubbles (MBs) 9,10 . Cavitation is one of the primary mechanisms of contrast agent-mediated sonothrombolysis 9 . Stable cavitation occurs when MBs oscillate and induce localized microstreaming and acoustic streaming.…”
One major challenge in current microbubble (MB) and tissue plasminogen activator (tPA)-mediated sonothrombolysis techniques is effectively treating retracted blood clots, owing to the high density and low porosity of retracted clots. Nanodroplets (NDs) have the potential to enhance retracted clot lysis owing to their small size and ability to penetrate into retracted clots to enhance drug delivery. For the first time, we demonstrate that a sub-megahertz, forward-viewing intravascular (FVI) transducer can be used for ND-mediated sonothrombolysis, in vitro. In this study, we determined the minimum peak negative pressure to induce cavitation with low-boiling point phase change nanodroplets and clot lysis. We then compared nanodroplet mediated sonothrombolysis to MB and tPA mediate techniques. The clot lysis as a percent mass decrease in retracted clots was 9 ± 8%, 9 ± 5%, 16 ± 5%, 14 ± 9%, 17 ± 9%, 30 ± 8%, and 40 ± 9% for the control group, tPA alone, tPA + US, MB + US, MB + tPA + US, ND + US, and ND + tPA + US groups, respectively. In retracted blood clots, combined ND- and tPA-mediated sonothrombolysis was able to significantly enhance retracted clot lysis compared with traditional MB and tPA-mediated sonothrombolysis techniques. Combined nanodroplet with tPA-mediated sonothrombolysis may provide a feasible strategy for safely treating retracted clots.
“…Sonothrombolysis has been particularly effective at treating unretracted blood clots and improving tPA treatment by incorporating ultrasound contrast agents such as microbubbles (MBs) 9,10 . Cavitation is one of the primary mechanisms of contrast agent-mediated sonothrombolysis 9 . Stable cavitation occurs when MBs oscillate and induce localized microstreaming and acoustic streaming.…”
One major challenge in current microbubble (MB) and tissue plasminogen activator (tPA)-mediated sonothrombolysis techniques is effectively treating retracted blood clots, owing to the high density and low porosity of retracted clots. Nanodroplets (NDs) have the potential to enhance retracted clot lysis owing to their small size and ability to penetrate into retracted clots to enhance drug delivery. For the first time, we demonstrate that a sub-megahertz, forward-viewing intravascular (FVI) transducer can be used for ND-mediated sonothrombolysis, in vitro. In this study, we determined the minimum peak negative pressure to induce cavitation with low-boiling point phase change nanodroplets and clot lysis. We then compared nanodroplet mediated sonothrombolysis to MB and tPA mediate techniques. The clot lysis as a percent mass decrease in retracted clots was 9 ± 8%, 9 ± 5%, 16 ± 5%, 14 ± 9%, 17 ± 9%, 30 ± 8%, and 40 ± 9% for the control group, tPA alone, tPA + US, MB + US, MB + tPA + US, ND + US, and ND + tPA + US groups, respectively. In retracted blood clots, combined ND- and tPA-mediated sonothrombolysis was able to significantly enhance retracted clot lysis compared with traditional MB and tPA-mediated sonothrombolysis techniques. Combined nanodroplet with tPA-mediated sonothrombolysis may provide a feasible strategy for safely treating retracted clots.
“…Sonothrombolysis is frequently used to aid in the improvement of thrombolytic therapy results [ 143 , 144 ]. This therapeutic method uses ultrasound's mechanical bioeffects to assist thrombolytic medicines to diffuse into blood clots and mechanically break down blood clots [ 89 , 145 ]. Fig.…”
Section: Novel Microbubble-based Treatment In Biomedicinementioning
Microbubbles are typically 0.5–10 μm in size. Their size tends to make it easier for medication delivery mechanisms to navigate the body by allowing them to be swallowed more easily. The gas included in the microbubble is surrounded by a membrane that may consist of biocompatible biopolymers, polymers, surfactants, proteins, lipids, or a combination thereof. One of the most effective implementation techniques for tiny bubbles is to apply them as a drug carrier that has the potential to activate ultrasound (US); this allows the drug to be released by US. Microbubbles are often designed to preserve and secure medicines or substances before they have reached a certain area of concern and, finally, US is used to disintegrate microbubbles, triggering site-specific leakage/release of biologically active drugs. They have excellent therapeutic potential in a wide range of common diseases. In this article, we discussed microbubbles and their advantageous medicinal uses in the treatment of certain prevalent disorders, including Parkinson's disease, Alzheimer's disease, cardiovascular disease, diabetic condition, renal defects, and finally, their use in the treatment of various forms of cancer as well as their incorporation with nanoparticles. Using microbubble technology as a novel carrier, the ability to prevent and eradicate prevalent diseases has strengthened the promise of effective care to improve patient well-being and life expectancy.
“…In recent years, microbubble enhanced sonothrombolysis has emerged as a promising therapeutic method for thrombotic diseases, and is endowed with the merits of ultrasound (US) and microbubbles (safety, ease of use, cost-effectiveness, and clinical availability) ( Ilovitsh et al, 2020 ; El Kadi et al, 2022 ). Extensive researches indicate that ultrasound and microbubbles may enhance thrombolysis through the mechanism of acoustic radiation, cavitation-mediated microstreaming, and microjet, facilitating enzymatic degradation and mechanical destruction of thrombus ( Goel and Jiang, 2020 ). One of the most exciting advantages the treatment modality prospects is the dosage reduction of thrombolytic agents, which may be critical for those high bleeding risk patients in which the use of thrombolytic agents is contradicted.…”
There is a need to improve the efficacy and safety of endovascular techniques in venous thrombotic diseases, and microbubble enhanced sonothrombolysis is a promising approach. However, whether endovascular low-frequency ultrasound (LFUS) can be utilized in microbubble enhanced sonothrombolysis is unclear. Here, we present a catheter-based thrombolytic system that combines unfocused low-frequency low-intensity ultrasound with novel fibrin-targeted drug-loaded bifunctional microbubbles. We develop an in vitro flow model and an in vivo rabbit inferior vena cava (IVC) thrombosis model to evaluate the safety and efficacy of the thrombolytic system. The results indicate that microbubble enhanced sonothrombolysis with endovascular LFUS treatment for 30 min is equally effective compared to pure pharmacologic treatment. Furthermore, the thrombolytic efficacy of this system is safely and substantially improved by the introduction of a fibrin-targeted drug-loaded bifunctional microbubble with a reduction of the fibrinolytic agent dosage by 60%. The microbubble enhanced endovascular LFUS sonothrombolysis system with excellent thrombolytic efficacy may serve as a new therapeutic approach for venous thrombotic diseases.
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