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Transdermal Delivery of a Tetrapeptide: Evaluation of Passive Diffusion

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Abstract

Skin penetration of the tetrapeptide Ac-Ala-Ala-Pro-Val-NH2 was assessed. This peptide sequence fits the P-P1 subsites of elastase and inhibits human neutrophil elastase competitively. Consequently this peptide may be therapeutically useful in a variety of inflammatory disorders, including psoriasis, in which elevated levels of human neutrophil elastase have been reported. Peptide penetration was assessed across whole human skin, whole skin with the stratum corneum removed by tape stripping and epidermis, which had been removed from the dermis by heat separation. The influence of 75 aqueous ethanol as a potential penetration enhancer of the tetrapeptide across epidermis was also assessed. The tetrapeptide did not penetrate whole human skin or epidermis, even under the influence of 75 aqueous ethanol. However, when the stratum corneum was removed tetrapeptide flux of 73.39 μg cm2 h−1 was achieved. The study demonstrates that the stratum corneum is the main barrier to tetrapeptide skin penetration and must be overcome if therapeutically relevant amounts of tetrapeptide are to be delivered to the skin.

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References

  1. Barry, B.W., Eur. J. Pharm. Sci., 14 (2001) 101.

    CAS  PubMed  Google Scholar 

  2. Mitragotri, S., Blankschtein, D. and Langer, R., Science, 269 (1995) 850.

    CAS  PubMed  Google Scholar 

  3. Smyth, H.D., Becket, G. and Mehta, S., J. Pharm. Sci., 91 (2002) 1296.

    Article  CAS  PubMed  Google Scholar 

  4. Sen, A., Daly, M.E. and Hui, S.W., Biochim. Biophys. Acta., 1564 (2002) 5.

    CAS  PubMed  Google Scholar 

  5. Al-Daraji, W.I., Grant, K.R., Ryan, K., Saxton, A. and Reynolds, N.J., J. Invest. Dermatol., 118 (2002) 779.

    Article  CAS  PubMed  Google Scholar 

  6. Bonifati, C., Clerico, R., Potenza, C.M. and Carlesimo, M., Acta. Derm. Venereol. Suppl. (Stockh), 146 (1989) 151.

    CAS  Google Scholar 

  7. Cooper, K.D., Voorhees, J.J., Fisher, G.J., Chan, L.S., Gupta, A.K. and Baadsgaard, O., J. Am. Acad. Dermatol., 23 (1990) 1318.

    CAS  PubMed  Google Scholar 

  8. Cooper, K.D., Baadsgaard, O., Ellis, C.N., Duell, E. and Voorhees, J.J., J. Invest. Dermatol., 94 (1990) 649.

    CAS  PubMed  Google Scholar 

  9. Duncan, J.I., Wakeel, R.A., Winfield, A.J., Ormerod, A.D. and Thomson, A.W., Acta Derm. Venereol., 73 (1993) 84.

    CAS  PubMed  Google Scholar 

  10. Choi, H.K., Flynn, G.L. and Amidon, G.L., J. Pharm. Sci., 84 (1995) 581.

    CAS  PubMed  Google Scholar 

  11. Guo, J., Ping, Q., Sun, G. and Jiao, C., Int. J. Pharm., 194 (2000) 201.

    Article  CAS  PubMed  Google Scholar 

  12. Rothbard, J.B., Garlington, S., Lin, Q., Kirschberg, T., Kreider, E., McGrane, P. L., Wender, P.A. and Khavari, P.A., Nat. Med., 6 (2000) 1253.

    Article  CAS  PubMed  Google Scholar 

  13. Holick, M.F., Chen, M.L., Kong, X.F. and Sanan, D.K., J. Invest. Dermatol. Symp. Proc., 1 (1996) 1.

    CAS  Google Scholar 

  14. Ozeki, M. and Tabata, Y., Tissue Eng., 8 (2002) 359.

    Article  CAS  PubMed  Google Scholar 

  15. Ozeki, M. and Tabata, Y., Biomaterials, 23 (2002) 2367.

    Article  CAS  PubMed  Google Scholar 

  16. Ito, C., Saitoh, Y., Fujita, Y., Yamazaki, Y., Imamura, T., Oka, S. and Suzuki, S., J. Cell. Physiol., 197 (2003) 272.

    Article  CAS  PubMed  Google Scholar 

  17. Seo, N., Tokura, Y., Nishijima, T., Hashizume, H., Furukawa, F. and Takigawa, M., Proc. Natl. Acad. Sci. USA, 97 (2000) 371.

    CAS  PubMed  Google Scholar 

  18. Svedman, P., Lundin, S. and Svedman, C., Lancet, 337 (1991) 1506.

    Article  CAS  PubMed  Google Scholar 

  19. Takigawa, M., Tokura, Y., Hashizume, H., Yagi, H. and Seo, N., Ann. N. Y. Acad. Sci., 941 (2001) 139.

    CAS  PubMed  Google Scholar 

  20. Draper, B.K., Komurasaki, T., Davidson, M.K. and Nanney, L.B., Wound Repair Regen., 11 (2003) 188.

    Article  PubMed  Google Scholar 

  21. Deodato, B., Arsic, N., Zentilin, L., Galeano, M., Santoro, D., Torre, V., Altavilla, D., Valdembri, D., Bussolino, F., Squadrito, F. and Giacca, M., Gene Ther., 9 (2002) 777.

    Article  CAS  PubMed  Google Scholar 

  22. Ehrlich, H.P. and Freedman, B.M., Cytokines Cell Mol. Ther., 7 (2002) 85.

    Article  CAS  PubMed  Google Scholar 

  23. Janoff, A., Annu. Rev. Med., 36 (1985) 207.

    Article  CAS  PubMed  Google Scholar 

  24. Toth, I., Int. J. Pharm., 125 (1995) 117.

    Article  CAS  Google Scholar 

  25. Schnolzer, M., Alewood, P., Jones, A., Alewood, D. and Kent, S.B., Int. J. Pept. Protein. Res., 40 (1992) 180.

    CAS  PubMed  Google Scholar 

  26. Sarin, V.K., Kent, S.B., Tam, J.P. and Merrifield, R.B., Anal. Biochem., 117 (1981) 147.

    Article  CAS  PubMed  Google Scholar 

  27. Vojkovsky, T., Pept. Res., 8 (1995) 236.

    CAS  PubMed  Google Scholar 

  28. Kligman, A. and Christophers, E., Arch. Dermatol., 88 (1963) 70.

    Google Scholar 

  29. Menon, G.K., Lee, S.H. and Roberts, M.S., in M.S. Roberts K.A. Walters, (eds.), Dermal Absorption and Toxicity Assessment. Marcel Dekker: New York, 1998, pp. 727.

    Google Scholar 

  30. Walters, K.A., Walker, M. and Olejnik, O., J. Pharm. Pharmacol., 40 (1988) 525.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Western Australian Biomedical Research Institute, School of Pharmacy, Curtin University, Perth, Western Australia, 6845, Australia

    Heather A. E. Benson, Rima Caccetta & Yan Chen

  2. School of Biological Chemistry and Pharmacy, University of Queensland, Brisbane, Queensland, Australia

    Philip Kearns & Istvan Toth

Authors
  1. Heather A. E. Benson
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  2. Rima Caccetta
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  3. Yan Chen
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  4. Philip Kearns
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  5. Istvan Toth
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Benson, H.A.E., Caccetta, R., Chen, Y. et al. Transdermal Delivery of a Tetrapeptide: Evaluation of Passive Diffusion. Int J Pept Res Ther 10, 615–620 (2003). https://doi.org/10.1007/s10989-004-2432-5

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