Pharmaceutical Research

, Volume 16, Issue 11, pp 1717–1721 | Cite as

Topical Drug Delivery in Humans with a Single Photomechanical Wave

  • Shun Lee
  • Nikiforos Kollias
  • Daniel J. McAuliffe
  • Thomas J. Flotte
  • Apostolos G. Doukas

Abstract

Purpose. Assess the feasibility ofin vivo topical drug delivery in humans with a single photomechanical wave.

Methods. Photomechanical waves were generated with a 23 nsec Q-switched ruby laser. In vivo fluorescence spectroscopy was used as an elegant non-invasive assay of transport of 5-aminolevulinic acid into the skin following the application of a single photomechanical wave.

Results. The barrier function of the human stratum corneum in vivo may be modulated by a single (110 nsec) photomechanical compression wave without adversely affecting the viability and structure of the epidermis and dermis. Furthermore, the stratum corneum barrier always recovers within minutes following a photomechanical wave. The application of the photomechanical wave did not cause any pain. The dose delivered across the stratum corneum depends on the peak pressure and has a threshold at ∼350 bar. A 30% increase in peak pressure, produced a 680% increase in the amount delivered.

Conclusions. Photomechanical waves may have important implications for transcutaneous drug delivery.

5-aminolevulinic acid ruby laser photoacoustics shock waves stress waves transdermal drug delivery 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

REFERENCES

  1. 1.
    R. Scheuplein. The skin as a barrier. In A. Jarrett (ed.), The physiology and pathophysiology of the skin, vol. 5, Academic Press, New York, 1978, pp. 1669–1692.Google Scholar
  2. 2.
    D. G. Kassan, A. M. Lynch, and M. J. Stiller. Physical enhancement of dermatologic drug delivery: inotophoresis and phonophoresis. J. Am. Acad. Dematol. 34:657–666 (1996).Google Scholar
  3. 3.
    J. C. Weaver. Electroporation: a general phenomenon for manipulating cells and tissues. J. Cell. Biochem. 51:426–435 (1993).Google Scholar
  4. 4.
    S. Singh and J. Singh. Transdermal drug delivery by passive diffusion and iontophoresis: a review. Med. Res. Rev. 13:569–621 (1993).Google Scholar
  5. 5.
    A. R. Williams. Phonphoresis: an in vivo evaluation using three topical anesthetic preparations. Ultrasonics 28:137–141 (1990).Google Scholar
  6. 6.
    J. C. McElnay, H. A. E. Benson, R. Harland, and J. Hadgraft. Phonophoresis of methyl nicotinate: a preliminary study to elucidate the mechanism of action. Pharm. Res. 10:1726–1731 (1993).Google Scholar
  7. 7.
    S. Mitragotri, D. Blankschtein, and R. Langer. Ultrasound-mediated transdermal protein delivery. Science 269:850–853 (1995).Google Scholar
  8. 8.
    N. N. Byl. The use of ultrasound as an enhancer for transcutaneous drug delivery: phonophoresis. Phys. Ther. 75:539–553 (1995).Google Scholar
  9. 9.
    D. Bommannan, G. K. Menon, H. Okuyama, P. M. Elias, and R. H. Guy. Sonophoresis. II. Examination of the mechanism(s) of ultrasound-enhanced transdermal drug delivery. Pharm. Res. 9:1043–1047 (1992).Google Scholar
  10. 10.
    S. Mitragotri, D. A. Edwards, D. Blankschtein, and R. Langer. A mechanistic study of ultrasonically-enhanced drug delivery. J. Pharm. Sci. 84:697–706 (1995).Google Scholar
  11. 11.
    M. W. Miller, D. L. Miller, and A. A. Brayman. A review of in vitro bioeffects of inertial ultrasonic cavitation from a mechanistic perspective. Ultrasound Med. Biol. 22:1131–1154 (1996).Google Scholar
  12. 12.
    A. G. Doukas and T. J. Flotte. Physical characteristics and biological effects of laser-induced stress waves. Ultrasound Med. Biol. 22:151–164 (1996).Google Scholar
  13. 13.
    G. R. ter Haar. Biological effects of ultrasound in clinical applications. In K.S. Suslick (ed.), Ultrasound its chemical physical biological effects, VCH Publishers, New York, 1988, pp. 305–320.Google Scholar
  14. 14.
    A. G. Doukas, D. J. McAuliffe, S. Lee, V. Venugopalan, and T. J. Flotte. Physical factors involved in stress-wave-induced cell injury: the effect of stress gradient. Ultrasound Med. Biol. 21:961–967 (1995).Google Scholar
  15. 15.
    S. Lee, T. Anderson, H. Zhang, T. J. Flotte, and A. G. Doukas. Alteration of cell membrane by stress waves in vitro. Ultrasound Med. Biol. 22:1285–1293 (1996).Google Scholar
  16. 16.
    D. J. McAuliffe, S. Lee, T. J. Flotte, and A. G. Doukas. Stress-wave-assisted transport through the plasma membrane in vitro. Lasers Surg. Med. 20:216–222 (1997).Google Scholar
  17. 17.
    S. Lee, D. J. McAuliffe, H. Zhang, Z. Xu, J. Taitelbaum, T. J. Flotte, and A. G. Doukas. Stress-wave-induced membrane permeation of red blood cells is facilitated by water channels. Ultrasound Med. Biol. 23:1089–1094 (1997).Google Scholar
  18. 18.
    S. Lee, D. J. McAuliffe, T. J. Flotte, N. Kollias, and A. G. Doukas. Photomechanical transcutaneous delivery of macromolecules. J. Invest. Dermatol. 111:925–929 (1998).Google Scholar
  19. 19.
    N. A. Monteiro-Riviere, B. G. Bristol, T. O. Manning, R. A. Rodgers, and J. E. Riviere. Interspecies and interregional analysis of the comparative histologic thickness and laser doppler blood flow measurements at five cutaneous sites in five species. J. Invest. Dermatol. 95:582–586 (1990).Google Scholar
  20. 20.
    L. E. Rhodes, M. M. Tsoukas, R. R. Anderson, and N. Kollias. Iontophoretic delivery of ALA provides a quantitative model for ALA pharmacokinetics and PpIX phototoxicity in human skin. J. Invest. Dermatol. 108:87–91 (1997).Google Scholar
  21. 21.
    B. A. Goff, R. Bachor, N. Kollias, and T. Hasan. Effects of photodynamic therapy with topical application of 5-aminolevulinic acid on normal skin of hairless guinea pigs. J. Photochem. Photobiol. B: Biol. 15:239–251 (1992).Google Scholar
  22. 22.
    D. X. G. Divaris, J. C. Kennedy, and R. H. Pottier. Phototoxic damage to sebaceous glands and hair follicles of mice after systemic administration of 5-aminolevulinic acid correlates with localized photoporphyrin IX fluorescence. Am. J. Pathol. 136:891–897 (1990).Google Scholar
  23. 23.
    R. R. Anderson. Optics of the skin. In H. W. Lim, N. A. Sotel, (eds.), Clinical Photomedicine, Marcel Dekker, New York, 1993, pp 19–35.Google Scholar
  24. 24.
    J.-M. Gaullier, M. Gèze, R. Santus, T. S. E. Melo, J.-C. Mazière, M. Bazin, P. Morlière, and L. Dubertret. Subcellular localization of and photosensitization by protoporphyrin IX in human keratinocytes and fibroblasts cultivated with 5-aminovulinic acid. Photochem. Photobiol. 62:114–122 (1995).Google Scholar
  25. 25.
    Y. Yashima, D. J. McAuliffe, and T. J. Flotte, Cell selectivity to laser-induced photoacoustic injury of skin. Lasers Surg. Med. 10:280–283 (1990).Google Scholar
  26. 26.
    G. M. Golden, J. E. McKie, and R. O. Potts. Role of stratum corneum lipid fluidity in transdermal drug flux. J. Pharm. Sci. 76:25–28 (1987).Google Scholar
  27. 27.
    W. J. Albery and J. Hadgraft. Percutaneous absorption: theoretical description. J. Pharm. Pharmacol. 31:129–139 (1979).Google Scholar
  28. 28.
    T. Arita, R. Hori, T. Anmo, M. Washitake, and T. Yajima. Studies on percutaneous absorption of drugs. I. Chem. Pharm. Bull. (Tokyo).18:1045–1049 (1970).Google Scholar
  29. 29.
    G. K. Menon, D. B. Bommannan, and P. M. Elias. High-frequency sonophoresis: permeation pathways and structural basis for enhanced permeability. Skin Pharmacol. 7:130–139 (1994).Google Scholar
  30. 30.
    G. K. Menon and P. M. Elias. Morphologic basis for a porepathway in mammalian stratum corneum. Skin Pharmacol. 10:235–246 (1997).Google Scholar

Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • Shun Lee
    • 1
  • Nikiforos Kollias
    • 1
  • Daniel J. McAuliffe
    • 1
  • Thomas J. Flotte
    • 1
  • Apostolos G. Doukas
    • 1
  1. 1.Department of Dermatology, Harvard Medical SchoolWellman Laboratories of Photomedicine, Massachusetts General HospitalBoston

Personalised recommendations