MECHANISTIC STUDY OF ULTRASONICALLY-ENHANCED TRANSDERMAL DRUG-DELIVERY
MECHANISTIC STUDY OF ULTRASONICALLY-ENHANCED TRANSDERMAL DRUG-DELIVERY
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DOI：
10.1002/jps.2600840607
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发表时间：
1995-06-01
影响因子：
3.8
通讯作者：
LANGER, R
中科院分区：
文献类型：
--
作者：
MITRAGOTRI, S;EDWARDS, DA;LANGER, R
虽然超声波已被证明可以增强多种药物的透皮转运，但这种现象背后的机制尚不清楚。在本文中，我们评估了各种超声相关的现象，包括空化，热效应，产生的对流速度，和机械效应，在超声增强经皮给药（超声促渗）中所起的作用。我们的实验结果表明，在所有超声相关的现象评价，空化起着主导作用，在超声促渗使用治疗超声（频率范围，1-3 MHz;强度范围，0-2 W/cm（2））。此外，共聚焦显微镜的结果表明，空化发生在角质层的角质细胞超声暴露后。假设空化气泡的振荡诱导角质层脂质双层中的紊乱，从而增强经皮转运。支持这一假设的证据是使用皮肤电阻测量。最后，建立了一个理论模型来预测超声波对药物透皮吸收的影响。该模型预测，超声促渗增强最直接地取决于被动渗透扩散系数，而不是通过皮肤的渗透系数。具体地，预期以相对慢的速率被动扩散通过皮肤的渗透物优先被超声增强。实验测得的超声促透皮传输增强7渗透，包括雌二醇，睾酮，孕酮，皮质酮，苯，丁醇，和咖啡因，同意定量与模型预测。这些实验和理论研究结果提供了定量的指导方针，估计超声促渗在促进经皮给药的功效。
Although ultrasound has been shown to enhance the transdermal transport of a variety of drugs, the mechanisms underlying this phenomenon are not clearly understood. In this paper, we evaluate the roles played by Various ultrasound-related phenomena, including cavitation, thermal effects, generation of convective velocities, and mechanical effects, in the ultrasonic enhancement of transdermal drug delivery (sonophoresis). Our experimental findings suggest that among all the ultrasound-related phenomena evaluated, cavitation plays the dominant role in sonophoresis using therapeutic ultrasound (frequency range, 1-3 MHz; intensity range, 0-2 W/cm(2)). Furthermore, confocal microscopy results indicate that cavitation occurs in the keratinocytes of the stratum corneum upon ultrasound exposure. It is hypothesized that oscillations of the cavitation bubbles induce disorder in the stratum corneum lipid bilayers, thereby enhancing transdermal transport. Evidence supporting this hypothesis is presented using skin electrical resistance measurements. Finally, a theoretical model is developed to predict the effect of ultrasound on the transdermal transport of drugs. The model predicts that sonophoretic enhancement depends most directly on the passive permeant diffusion coefficient, rather than on the permeability coefficient through the skin. Specifically, permeants passively diffusing through the skin at a relatively slow rate are expected to be preferentially enhanced by ultrasound. The experimentally measured sonophoretic transdermal transport enhancement for seven permeants, including estradiol, testosterone, progesterone, corticosterone, benzene, butanol, and caffeine, agree quantitatively with the model predictions. These experimental and theoretical findings provide quantitative guidelines for estimating the efficacy of sonophoresis in enhancing transdermal drug delivery.