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Frequency Dependence of Sonophoresis

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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 sought to determine the dependence of low-frequency sonophoresis on ultrasound frequency, intensity and energy density.

Methods. Pig skin was exposed to low-frequency ultrasound over a range of ultrasound frequency and intensity conditions. The degree of skin permeabilization was measured using its conductivity. Imaging experiments were also carried out to visualize the transport pathways created by ultrasound.

Results. The data showed that for each frequency (in the range of 19.6-93.4 kHz), there exists a threshold intensity below which no detectable conductivity enhancement was observed. The threshold intensity increased with frequency. It is feasible to achieve the desired conductivity (permeability) enhancement regardless of the choice of frequency, although the necessary energy density is higher at higher frequencies. Low frequencies (∼20 kHz) induced localized transport compared to a more dispersed effect seen with higher frequencies (∼58.9 kHz).

Conclusions. This study provides a quantitative understanding of the effects of low-frequency ultrasound on skin permeability.

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REFERENCES

  1. G. A. Simon and H. I. Maibach. The pig as an experimental animal model of percutaneous permeation in man: qualitative and quantative observations—an overview. Skin Pharmacol. Appl. Skin Physiol. 13:229-234 (2000).

    Google Scholar 

  2. P. M. Elias. Epidermal lipids, barrier function, and desquamation. J. Invest. Dermatol. 80:44-49 (1983).

    Google Scholar 

  3. T. M. Suhonen, J. A. Bouwstra, and A. Urtti. Chemical enhancement of percutaneous absorption in relation to stratum corneum structural alteration. J. Control. Release 59:149-161 (1999).

    Google Scholar 

  4. B. Forslind, S. Engstrom, J. Engblom, and L. Norlen. A novel approach to the understanding of human barrier function. J. Dermatol. Sci. 14:115-125 (1997).

    Google Scholar 

  5. K. A. Walters and J. Hadgraft. Pharmaceutical Skin Penetration Enhancement, 59, Marcel Dekker, New York, 1993

    Google Scholar 

  6. R. B. Walker and E. W. Smith. The role of percutaneous penetration enhancers. Adv. Drug Deliv. Rev. 18:295-301 (1996).

    Google Scholar 

  7. Y. N. Kalia and R. H. Guy. Interaction between penetration enhancers and iontophoresis: Effect on human skin impedance in vivo. J. Control. Release 44:33-42 (1997).

    Google Scholar 

  8. M. R. Prausnitz, V. Bose, R. Langer, and J. C. Weaver. Electroporation of mammalian skin: A mechanism to enhance transdermal drug delivery. Proc. Natl. Acad. Sci. 90:10504-10508 (1993).

    Google Scholar 

  9. D. Levy, J. Kost, Y. Meshulam, and R. Langer. Effect of ultrasound on transdermal drug delivery to rats and guinea pigs. J. Clin. Invest. 83:2974-2978 (1989).

    Google Scholar 

  10. S. Mitragotri, D. Blankschtein, and R. Langer. Transdermal drug delivery using low frequency sonophoresis. Pharm. Res. 13:411-420 (1996).

    Google Scholar 

  11. S. Mitragotri, D. Blankschtein, and R. Langer. Ultrasound-mediated transdermal protein delivery. Science 269:850-853 (1995).

    Google Scholar 

  12. W. Gaertner. Frequency dependence of acoustic cavitation. J. Acoust. Soc. Am. 26:977-980 (1954).

    Google Scholar 

  13. S. Mitragotri, D. Ray, J. Farrell, H. Tang, B. Yu, J. Kost, D. Blankschtein, and R. Langer. Synergistic effect of Low-Frequency Ultrasound and Sodium Lauryl Sulfate on Transdermal Transport. J. Pharm. Sci. 89:892-900 (2000).

    Google Scholar 

  14. S. Mitragotri, J. Farrell, H. Tang, T. Terahara, J. Kost, and R. Langer. Determination of threshold energy dose for ultrasound-induced transdermal drug transport. J. Control. Release 63:41-52 (2000).

    Google Scholar 

  15. K. S. Suslick. Ultrasound: Its chemical, physical, and biological effects, VCH Publishers, New York, 1989.

    Google Scholar 

  16. E. A. Neppiras. Subharmonic and other low-frequency emission from bubbles in sound irradiated liquids. J. Acoust. Soc. Am. 46:587-601 (1968).

    Google Scholar 

  17. J. Liu, T. N. Lewis, and M. R. Prausnitz. Non-invasive assessment and control of ultrasound mediated membrane permeabilization. Pharm. Res. 15:918-924 (1998).

    Google Scholar 

  18. U. F. Pliquett, T. E. Zewert, T. Chen, R. Langer, and J. C. Weaver. Imaging of fluorescent molecule and small ion transport through human stratum corneum during high voltage pulsing: localized transport regions are involved. Biophys. Chemist. 58: 185-204 (1996).

    Google Scholar 

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Tezel, A., Sens, A., Tuchscherer, J. et al. Frequency Dependence of Sonophoresis. Pharm Res 18, 1694–1700 (2001). https://doi.org/10.1023/A:1013366328457

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