Department of Biomedical Engineering, Yonsei University, Wonju, Korea.
Ultrasound Med Biol. 2012 Apr;38(4):642-50. doi: 10.1016/j.ultrasmedbio.2011.12.015. Epub 2012 Feb 16.
Sonophoresis temporally increases skin permeability such that various medications can be delivered noninvasively. Previous sonophoresis studies have suggested that cavitation plays an important role in enhancing transdermal drug delivery (TDD). In this study, the feasibility of controlled cavitation using ultrasound contrast agents (UCAs) at high frequency was explored through in vivo experiments in a rat model. Two commercially available UCAs, SonoVue® and Definity®, were used at 2.47 MHz and 1.12 MHz, respectively. Fluorescein isothiocyanate (FITC)-dextran with 0.1% UCA was used as the drug to be delivered through the skin. Ultrasound with a 10 ms pulse and a 1% duty cycle at 1 MPa acoustic pressure for 30 min was applied in all sonication sessions. The efficacy of sonophoresis with UCAs was quantitatively analyzed using an optical imaging system that was used to count photons emitted from fluorescein. The results showed that the proposed sonophoresis method significantly improved drug penetration compared with the traditional sonophoresis method with 4 kD, 20 kD and 150 kD FITC-dextrans at 1.12 MHz, and with 4 kD and 20 kD FITC-dextrans at 2.47 MHz. Sonophoresis for TDD was performed more effectively with the aid of UCAs. Sonophoresis with UCAs has excellent potential for broad applications in drug delivery for diseases requiring the chronic administration of medications such as diabetes.
声透法可暂时增加皮肤的通透性，从而实现各种药物的无创输送。先前的声透法研究表明，空化在增强经皮药物输送（TDD）方面起着重要作用。在这项研究中，通过在大鼠模型中的体内实验，探索了高频超声对比剂（UCAs）控制空化的可行性。使用了两种市售的 UCAs，SonoVue®和 Definity®，分别在 2.47 MHz 和 1.12 MHz 下使用。将 0.1%UCA 的荧光素异硫氰酸酯（FITC）-葡聚糖用作要输送到皮肤中的药物。所有声处理过程中均使用 10 ms 脉冲、1%占空比和 1 MPa 声压的超声，持续 30 min。使用光学成像系统对声透法加 UCAs 的效果进行定量分析，该系统用于计数从荧光素发射的光子。结果表明，与传统的 1.12 MHz 下的 4 kD、20 kD 和 150 kD FITC-葡聚糖以及 2.47 MHz 下的 4 kD 和 20 kD FITC-葡聚糖的声透法相比，所提出的声透法方法显著提高了药物渗透。在 UCAs 的辅助下，TDD 的声透法更有效。声透法加 UCAs 具有在需要慢性药物治疗的疾病（如糖尿病）中进行药物输送的广泛应用的巨大潜力。
