J Surg Ultrasound.  2023 Nov;10(2):32-41. 10.46268/jsu.2023.10.2.32.

Effects of Ultrasound Targeted Destruction of Echogenic Nanobubbles Containing Doxorubicin in Rat Liver

• Park JH
• Park IY

• KMID: 2553148
• DOI: http://doi.org/10.46268/jsu.2023.10.2.32

Abstract

Ultrasound is a widely used diagnostic medical imaging modality, and its therapeutic potential has recently been reported. This study examined whether ultrasound irradiation causes nanobubble destruction and identified the most effective frequency and duration of ultrasound for doxorubicin delivery in rat liver under ultrasound-targeted nanobubble destruction. Rats underwent an intravenous nanobubble injection via the caudal vein. An ultrasound probe was applied to the rat liver. The rats were divided into different groups based on the frequency. Fluorescence images were acquired using an IVIS® system. Laboratory tests were performed to determine the serum levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), total bilirubin, and creatinine. Under ultrasound irradiation, more nanobubbles were destroyed, and the doxorubicin uptake was increased in the rat liver (P ＜ 0.05). The 5 MHz group showed an increased fluorescence efficiency in the liver (P ＜ 0.05). Based on the duration of ultrasound irradiation, the 5, 10, and 13 MHz groups showed an increased fluorescence efficiency in the liver compared to the control group (P ＜ 0.05). There was no significant difference between the 15- and 30-minute groups. The other organs showed no significant differences compared to the control group. The groups to which ultrasound was applied showed increased serum AST and ALT levels, but the effects did not last for 30 min. Ultrasound-targeted nanobubble destruction was effective for doxorubicin delivery in the rat liver. The most effective ultrasound frequency and irradiation duration were 5 MHz and 15 min, respectively.

Keyword

Microbubble; Ultrasound; Frequency; Duration; Doxorubicin

Figure

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  Fig. 1 Schematic representation of synthesis and action of echogenic nanobubbles.

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  Fig. 2 Transmission electron microscope image (A) and size distribution (B) of echogenic nanobubbles.

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  Fig. 3 View of experiment. After general anesthesia, the rat was placed in supine position. The abdominal wall was prepared for the experiment. a: ultrasound probe, b: inhalation mask.

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  Fig. 4 Sonographic images of the rat liver. (A) no ultrasound group, (B) 5 MHz group, (C) 10 MHz group, (D) 13 MHz group, IVC: inferior vena cava, A: aorta, HV: hepatic vein.

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  Fig. 5 Fluorescence images of rat organs according to frequency.

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  Fig. 6 Fluorescence efficiency in different organ before and after 5 MHz ultrasound irradiation.

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  Fig. 7 Change in distribution of fluorescence efficiency in organs after 5 MHz ultrasound irradiation.

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