Abstract
Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the concentration of microbubbles in case stable cavitation is predominant.
Highlights
Sonophoresis, which uses ultrasound for transdermal drug delivery, is a non-invasive, painless method and is independent of electrical drug characteristics [1,2,3]
We evaluated sonophoresis in the presence of engineered microbubbles which are widely used as ultrasound imaging contrast (UCA) agent [19, 21, 22]
The dependence on UCA concentration for sonophoresis was evaluated though two types of experiments
Summary
Sonophoresis, which uses ultrasound for transdermal drug delivery, is a non-invasive, painless method and is independent of electrical drug characteristics [1,2,3]. Sonophoresis can increase skin permeability to various drugs, including hydrophilic, lipophilic permeants, and large molecular weight compounds [4, 5]. In TDD using sonophoresis, the nuclei of cavitation are mostly believed to be small bubbles trapped between the skin surface and transducer. Cavitation appears to cause disordering of the lipid bilayers and the formation of aqueous channels in the skin. Recovery of the skin barrier properties was indirectly evaluated by measurement of transdermal water flux and electrical resistance after ultrasound exposure. The result indicated that skin surface exposed to ultrasound eventually appears to recover to normal intact form within a day [12]
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