Study on Temperature Field of Biological Tissues During Low-Frequency Ultrasound TransdermalDrug Delivery
Zhao Ke1, He Bingbing1, Zhang Yufeng1,2#*
1(Department of Electronic Engineering, Information School, Yunnan University, Kunming 650091, China) 2(Dianchi College of Yunnan University, Kunming 650228, China)
Abstract:In the process of low-frequency ultrasound transdermal drug delivery, effects of the ultrasound frequency parameters on the temperature of biological tissues are still unclear. In this paper, finite element analysis (finite element analysis and in vitro experiments of biological tissues) was used to study the effects of low-frequency ultrasound of different frequencies on the temperature distribution of biological tissues, aiming to achieve the therapeutic effect without causing thermal damage to the skin layer of biological tissues. In order to verify the effectiveness of the model, a self-developed low-frequency ultrasonic energy output device was used to perform anex vivo pork test, and the temperature field distribution and temporal temperature changes of the isolated tissues under low-frequency ultrasound were monitored by a FLIR infrared thermal imager. The results of finite element analysis showed that after 20 minutes of low-frequency ultrasound, the temperature inside the biological tissue decreased with the increase of ultrasound frequency, and the temperature of the fat layer was the highest, reaching 40.89℃, and the temperature change of the skin layer displayed by the domain probe met the safety requirements of transdermal drug administration of low-frequency ultrasound. Different ultrasound frequency parameters have a significant effect on the temperature change of biological tissues under the action of low-frequency ultrasound. The in vitro experiments under the same ultrasonic parameter settings showed that the temperature field distribution and its maximum temperature value in the biological tissue were basically consistent with the values detected by the domain point probe of the simulation experiment, and the temperature difference was within 1℃, which is within a reasonable error range. From the simulation results and in vitro experimental results, it could be seen that the above ultrasound parameter settings did not cause thermal damage to skin tissue and achieved the purpose of effective treatment. The model established in this study is expected to predict the temperature change in tissues and provide a reference for the action time and parameter setting of low-frequency ultrasound transdermal drug delivery.
赵可, 何冰冰, 张榆锋. 低频超声透皮给药过程中的生物组织温度场研究[J]. 中国生物医学工程学报, 2026, 45(1): 61-69.
Zhao Ke, He Bingbing, Zhang Yufeng. Study on Temperature Field of Biological Tissues During Low-Frequency Ultrasound TransdermalDrug Delivery. Chinese Journal of Biomedical Engineering, 2026, 45(1): 61-69.
[1] Cetingül MP, Herman C. A heat transfer model of skin tissue for the detection of lesions: sensitivity analysis[J]. Physics in Medicine and Biology, 2010, 55(19): 5933-5951. [2] Oberli MA, Schoellhammer CM, Langer R, et al. Ultrasound-enhanced transdermal delivery: recent advances and future challenges[J]. Therapeutic Delivery, 2014, 5(7): 843-857. [3] Ramadon D, McCrudden MTC, Courtenay AJ, et al. Enhancement strategies for transdermal drug delivery systems: current trends and applications[J]. Drug Delivery and Translational Research, 2021, 12(4): 1-34. [4] Louis F, Fujii N, Katsuyama M, et al. Effects of radiofrequency and ultrasound on the turnover rate of skin aging components (skin extracellular matrix and epidermis) via HSP47-induced stimulation[J]. Biochemical and Biophysical Research Communications, 2020, 525(1): 73-79. [5] Emami S, Shayanfar A. Deep eutectic solvents for pharmaceutical formulation and drug delivery applications[J]. Pharmaceutical Development and Technology, 2020, 25(7): 779-796. [6] Telichko AV, Wang Huaijun, Bachawal S, et al. Therapeutic ultrasound parameter optimization for drug delivery applied to a murine model of hepatocellular carcinoma[J]. Ultrasound in Medicine & Biology, 2021, 47(2): 309-322. [7] Murugaiyan A, Sahoo AK, Rao PB, et al. Effect of 5% EMLA cream on postoperative sore throat in adults following general endotracheal anesthesia: a randomized placebo-controlled study[J]. Anesthesia & Analgesia, 2023, 136(2): 338-345. [8] 梁松, 张义民. 超声清洗换能器设计及性能分析[J]. 振动. 测试与诊断, 2013, 33(S2): 87-90,221. [9] 彭瀚旻, 陈致钧, 卢鹏辉, 等. 低频超声透皮给药系统压电-声-热计算模型[J].振动.测试与诊断, 2015, 35(6): 1037-1043, 1197. [10] 彭瀚旻, 喻伯平, 毛婷, 等. 低频超声透皮给药过程流场影响分析[J]. 振动.测试与诊断, 2016, 36(6): 1109-1115, 1237. [11] Huang JY, Su FF, Gaffney KD, et al. Skin dose estimation using virtual structures for Contura Multi-Lumen Balloon breast brachytherapy[J]. Brachytherapy, 2018, 17(6): 956-965. [12] Xing Xuejian; Zhao Shaojing; Xu Ting, et al. Advances and perspectives in organic sonosensitizers for sonodynamic therapy[J]. Coordination Chemistry Reviews, 2021, 445:214087. [13] 章东. 医学超声基础[M]. 北京:科学出版社, 2014. [14] 尹昌, 刘晓宙, 龚秀芬, 等. 超声引起的双层生物组织中的温度场研究[J]. 中国生物医学工程学报, 2009, 28(1): 42-47. [15] 程东旭, 岳晴雯, 周志勇, 等. 基于PZFlex的1-3压电复合材料横向振动模仿真[J]. 压电与声光, 2022, 44(3): 357-360, 367. [16] Wu Shaowei; Wan Detao; Jiang Chen, et al. A finite strain model for multi-material, multi-component biomechanical analysis with total Lagrangian smoothed finite element method[J]. International Journal of Mechanical Sciences, 2023, 243 (1):108017. [17] Shih TC, Kou HS, Liauh CT, et al. Thermal models of bioheat transfer equations in living tissue and thermal dose equivalence due to hyperthermia[J]. Biomedical Engineering: Applications, Basis and Communications, 2002, 14(2): 86-96. [18] 臧连儒, 周宇, 康佳, 等. 电极间距与电极直径对恒功率下双极射频熔脂效果影响的研究[J]. 中国生物医学工程学报, 2020, 39(5): 566-576. [19] Song JW, Ryu HJ, Bai WB, et al. Bioresorbable, wireless, and battery-free system for electrotherapy and impedance sensing at wound sites[J]. Science Advances, 2023, 9(8): eade4687. [20] Makvandi P, Kirkby M, Hutton ARJ, et al. Engineering microneedle patches for improved penetration: analysis, skin models and factors affecting needle insertion[J]. Nano-Micro Letters, 2021, 13(1): 93-93. [21] Singh S, Melnik R. Thermal ablation of biological tissues in disease treatment: A review of computational models and future directions[J]. Electromagnetic Biology and Medicine, 2020, 39(2): 49-88. [22] 孙彪, 郭霞生, 屠娟, 等. 用于活体温度评估的非线性超声热应变模型[J]. 应用声学, 2021, 40(1): 44-50. [23] Rudenko OV. Nonlinear acoustics in medicine: a review[J]. Physics of Wave Phenomena, 2022, 30(2): 73-85.