Transdermal drug delivery using low-frequency sonophoresis
Transdermal drug delivery using low-frequency sonophoresis
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DOI：
10.1023/a:1016096626810
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发表时间：
1996-03-01
影响因子：
3.7
通讯作者：
Langer, R
中科院分区：
文献类型：
--
作者：
Mitragotri, S;Blankschtein, D;Langer, R
目的.治疗性超声波（频率：1-3 MHz，强度：0-2 W/cm（2））的应用增强了药物的透皮转运，尽管通常不到10倍。在本文中，我们表明，应用超声波在20千赫诱导的经皮转运增强高达1000倍以上的治疗性超声波。通过体外（人尸体表皮）和体内（无毛大鼠皮肤）渗透实验，研究低频超声对透皮吸收的影响。低频超声的应用（20 KHz，125 mW/ cm（2），每秒施加100 msec脉冲）增强了几种渗透物的透皮转运，包括雌二醇、水杨酸、皮质酮、蔗糖、醛固酮、水和丁醇，通过人尸体皮肤的系数在3至3000的范围内，并且水杨酸通过无毛大鼠体内皮肤的系数高达300。低频超声波不会引起皮肤屏障特性的长期破坏（体外）或对无毛大鼠的活体皮肤造成损害。在一个机制的水平上，它是假设，应用低频超声增强通过水通道在SC产生的空化诱导的双层无序的经皮运输。支持这一假设提供了使用低频声发射的实验和理论分析。结论。低频超声波比治疗性超声波更能促进药物的透皮吸收。
Purpose. Application of therapeutic ultrasound (frequency: 1-3 MHz and intensity: 0-2 W/cm(2)) enhances transdermal drug transport, although typically by a factor of less than 10. In this paper, we show that application of ultrasound at 20 KHz induces transdermal transport enhancements of up to 1000 times higher than those induced by therapeutic ultrasound.Methods. In vitro (human cadaver epidermis) as well as in vivo (hairless rat skin) permeation experiments were performed to assess the effect of low-frequency ultrasound on transdermal transport.Results. Application of low-frequency ultrasound (20 KHz, 125 mW/ cm(2), 100 msec pulses applied every second) enhanced transdermal transport of several permeants, including estradiol, salicylic acid, corticosterone, sucrose, aldosterone, water, and butanol, across human cadaver skin by a factor in the range of 3 to 3000 and that of salicylic acid across hairless rat skin in vivo by a factor of up to 300. Low-frequency ultrasound did not induce a long-term toss of the barrier properties of the skin (in vitro) or damage to living skin of hairless rats. At a mechanistic level, it is hypothesized that application of low-frequency ultrasound enhances transdermal transport through aqueous channels in the SC generated by cavitation-induced bilayer disordering. Support for this hypothesis is provided using experimental and theoretical analyses of low-frequency sonophoresis.Conclusions. Low-frequency ultrasound enhances transdermal transport of drugs more effectively than that induced by therapeutic ultrasound.