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A Theoretical Analysis of Low-Frequency Sonophoresis: Dependence of Transdermal Transport Pathways on Frequency and Energy Density

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Abstract

Purpose. Application of low-frequency ultrasound has been shown to increase skin permeability, thereby facilitating delivery of macromolecules (low-frequency sonophoresis). In this study, we seek to determine the dependence of transport pathways during low-frequency sonophoresis on ultrasound parameters.

Methods. Pig skin is exposed to low-frequency ultrasound over a range of frequencies to achieve different skin resistivities. The porous pathway model is used to study the dependence of average pore size, porosity, and tortuosity on ultrasound parameters. Imaging experiments are also carried out to visualize the transport pathways created by ultrasound.

Results. The data show that the average pore size, determined from the porous pathway model, does not depend on application frequency. Both in the presence and absence of ultrasound the average pore size determined from mannitol delivery is the same (28 ± 12 Å). With the application of ultrasound the skin porosity could be increased by up to 1700-fold. The effect of ultrasound on skin is heterogeneous thereby creating localized transport pathways (LTP). The porosity of these transport pathways is of the same order of magnitude as that of the dermis.

Conclusions. With this study it is shown that low-frequency ultrasound increases skin permeability by increasing skin porosity rather than by increasing the size of the pores that are responsible for permeant delivery.

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Authors and Affiliations

  1. Department of Chemical Engineering, University of California Santa Barbara, Santa Barbara, California, 93106

    Ahmet Tezel & Samir Mitragotri

  2. Department of Chemistry, Santa Barbara City College, Santa Barbara, California, 93109

    Ashley Sens

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  1. Ahmet Tezel
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  2. Ashley Sens
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  3. Samir Mitragotri
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Correspondence to Samir Mitragotri.

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Tezel, A., Sens, A. & Mitragotri, S. A Theoretical Analysis of Low-Frequency Sonophoresis: Dependence of Transdermal Transport Pathways on Frequency and Energy Density. Pharm Res 19, 1841–1846 (2002). https://doi.org/10.1023/A:1021493424737

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