SONOPHORESIS .1. THE USE OF HIGH-FREQUENCY ULTRASOUND TO ENHANCE TRANSDERMAL DRUG DELIVERY
SONOPHORESIS .1. THE USE OF HIGH-FREQUENCY ULTRASOUND TO ENHANCE TRANSDERMAL DRUG DELIVERY
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DOI：
10.1023/a:1015808917491
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发表时间：
1992-04-01
影响因子：
3.7
通讯作者：
GUY, RH
中科院分区：
文献类型：
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作者：
BOMMANNAN, D;OKUYAMA, H;GUY, RH
以前尝试使用超声波（小于或等于1 MHz的频率和1至3 W/cm 2的强度），以提高经皮给药（所谓的超声促渗）产生了不一致的结果。超声在组织中传播的理论分析预测，高频超声（> 1 MHz）将增加角质层（SC）（通常是经皮渗透的限速屏障）中的能量沉积浓度。这一假设进行了测试，通过比较被动经皮给药的水杨酸与超声波的影响下，在2-，10-，和16-MHz的频率;测量进行了体内无毛豚鼠。通过测定（1）SC胶带条中存在的水杨酸和（2）尿液中消除的水杨酸的量，对吸收的总药物进行定量。在2 MHz下超声促渗20 min，与被动扩散相比，水杨酸的递送没有显著增加;另一方面，在10和16 MHz下用超声处理，显著提高了水杨酸的转运，分别为4倍和2.5倍。在10和16 MHz的超声波数据的动力学分析也表明，与经皮给药（TDD）的扩散滞后时间减少。一个较短的时间段（5分钟）的超声波电泳再次导致增强TDD（相对于相应的控制）在较高的频率;交付的剂量，增强的水平，但是，低于20分钟的治疗后。在单独的一系列实验中，表明（a）超声不改变水杨酸从所用凝胶制剂中的释放动力学和（B）用10和16 MHz的超声预处理皮肤降低了皮肤屏障功能，使得与没有超声促渗预处理的被动转运相比，水杨酸的随后递送增强。由此可见，超声促渗的增强效果是由于超声对角质层的直接作用（推测）。
Previous attempts to use ultrasound (less-than-or-equal-to 1-MHz frequency and 1 to 3-W/cm2 intensity) to enhance transdermal drug delivery (so-called sonophoresis) have produced inconsistent results. Theoretical analysis of ultrasound propagation in tissue predicts that higher-frequency ultrasound (> 1 MHz) will increase the concentration of energy deposition in the stratum corneum (SC) (typically, the rate-limiting barrier to percutaneous penetration). This hypothesis was tested by comparing the passive transdermal delivery of salicylic acid with that under the influence of ultrasound at 2-, 10-, and 16-MHz frequency; measurements were performed in vivo in hairless guinea pigs. Total drug absorbed was quantified by determining the amount of salicylic acid (1) present in SC tape strips and (2) eliminated in urine. Sonophoresis for 20 min at 2 MHz caused no significant increase in salicylic acid delivery over passive diffusion; treatment with ultrasound at 10 and 16 MHz, on the other hand, significantly elevated salicylic acid transport, by 4-fold and 2.5-fold, respectively. Kinetic analysis of the sonophoretic data at 10 and 16 MHz also revealed that the diffusion lag time associated with transdermal drug delivery (TDD) was reduced. A shorter period (5 min) of sonophoresis again resulted in enhanced TDD (relative to the corresponding control) at the higher frequencies; the delivered dose, and the level of enhancement, however, were lower than those after the 20-min treatment. In a separate series of experiments, it was shown that (a) ultrasound did not alter the release kinetics of salicylic acid from the gel formulation used and (b) pretreatment of the skin with ultrasound at 10 and 16 MHz lowered skin barrier function such that the subsequent delivery of salicylic acid was enhanced compared to passive transport without sonophoresis pretreatment. It follows that the enhancing effect of sonophoresis is due to a direct effect of ultrasound on (presumably) the stratum corneum.