Enhanced thrombolysis by endovascular low-frequency ultrasound with bifunctional microbubbles in venous thrombosis: in vitro and in vivo study

Abstract

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.

Ultrasound Combined With Continuous Microbubble Injection to Enhance Catheter‐Directed Thrombolysis in Vitro and in Vivo

“…Previous studies have primarily focused on the role of acoustic parameters and microbubble properties in this process. 10,[14][15][16][17][18][19] However, limited studies have investigated the impact of microbubble perfusion mode on CDT. Therefore, this study evaluated the thrombolytic effect of two types of microbubble perfusion modes (continuous injection versus bolus injection) in vitro.…”

“…Ultrasound combined with microbubbles has the potential to enhance the effectiveness of CDT and reduce the risk of treatment‐related bleeding. Previous studies have primarily focused on the role of acoustic parameters and microbubble properties in this process 10,14–19 . However, limited studies have investigated the impact of microbubble perfusion mode on CDT.…”

“…Several studies have revealed that the mechanism of ultrasound combined with microbubbles to enhance thrombolysis is cavitation-mediated acoustic radiation, microjet, and microstreaming, which facilitates enzymatic degradation and mechanical destruction of thrombus, [11][12][13] and these responses are mainly regulated by ultrasound parameters and microbubble. However, current studies mainly report the influence of ultrasound intensity and microbubble property on CDT, 10,[14][15][16][17][18][19] and few studies focus on the influence of microbubble perfusion mode on CDT.…”

Smart Hydrogel Swelling State Detection Based on a Power-Transfer Transduction Principle

“…Catheters are widely used in medical procedures and applications such as cardiac surgeries, ultrasound-based tumor treatment, and administration of medication. , Equipping these standard medical tools with additional sensing capabilities to enhance and extend their performance is an emerging field of research. Most developments so far focus on improving navigation and handling of catheters inside blood vessels to minimize tissue contact and resulting damage .…”

A Self-Healing Optoacoustic Patch with High Damage Threshold and Conversion Efficiency for Biomedical Applications

“…Ultrasonic devices are widely utilized in imaging [ 1 ], sonodynamic therapy [ 2 ], catalyst synthesis [ 3 ], drug delivery [ 4 ], neuromodulation [ 5 – 7 ], thrombolysis [ 8 ], and wireless energy harvesting [ 9 – 11 ]. In recent years, optoacoustic devices have attracted significant attention compared with traditional piezoelectric devices, due to their unique advantages such as simple preparation, electromagnetic compatibility, and high bandwidth [ 12 – 19 ].…”