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Effect of Electroporation on Transdermal lontophoretic Delivery of Luteinizing Hormone Releasing Hormone (LHRH) in Vitro

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Abstract

Electroporation, the creation of transient, enhanced membrane permeability using short duration (microseconds to millisecond) electrical pulses, can be used to increase transdermal drug delivery. The effect of an (electroporative) electric pulse (1000 V, τ = 5 msec) on the iontophoretic transport of LHRH through human skin was studied in vitro. Fluxes achieved with and without a pulse under different current densities (0- 4 mA/cm2) were compared. The results indicated that the application of a single pulse prior to iontophoresis consistently yielded higher fluxes (5—10 times the corresponding iontophoretic flux). For example, at 0.5 mA/cm2 fluxes were 0.27 ± 0.08 and 1.62 ± 0.05 µg/hr/cm2 without and with the pulse, respectively. At each current density studied, the LHRH flux decreased after iontophoresis, approaching pre-treatment values. The results show that electroporation can significantly and reversibly increase the flux of LHRH through human skin. These results also indicate the therapeutic utility of using electroporation for enhanced transdermal transport.

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REFERENCES

  1. M. Heit, P. Williams, F. Jayes, S. Chang, and J. Riviere. Transdermal iontophoretic peptide delivery: in vitro and in vivo studies with leuteinizing hormone releasing hormone. J. Pharm. Sci. 82: 240–243(1993).

    Google Scholar 

  2. B. R. Meyer, W. Kreis, J. Eschbach, V. O'Mara, S. Rosen, and D. Sibalis. Successful transdermal administration of therapeutic doses of a polypeptide to normal human volunteers. Clinical Pharmacology and Therapeutics. 44: 607–612(1988).

    Google Scholar 

  3. V. Srinivasan, M.-H. Su, W. I. Higuchi, and C. R. Behl. Iontophoresis of polypeptides: Effect of ethanol pretreatment of human skin. J. Pharm. Sci. 79: 588–591(1990).

    Google Scholar 

  4. L. Miller, C. Kolaskie, G. Smith, and J. Rivier. Transdermal iontophoresis of gonadotrophin releasing hormone (LHRH) and two analogues. J. Pharm. Sci. 79: 490–493(1990).

    Google Scholar 

  5. R. Burnette, and D. Marrero. Comparison between the iontophoretic and passive transport of thyrotropin releasing hormone across excised nude mouse skin. J. Pharm. Sci. 75: 738–743 (1986).

    Google Scholar 

  6. R. Meyer, H. Katzeff, J. Eschbach, J. Trimmer, S. Zacharias, S. Rosen, and D. Sibalis. Transdermal delivery of human insulin to albino rabbits using electrical current. The American Journal of the Medical Sciences. 297: 321–325(1989).

    Google Scholar 

  7. O. Siddiqui, Y. Sun, J.-C. Liu, and Y. W. Chien. Facilitated transdermal transport of insulin. J. Pharm. Sci. 76: 341–345 (1987).

    Google Scholar 

  8. V. Srinivasan, W. I. Higuchi, S. M. Sims, A. H. Ghanem, and C. R. Behl. Transdermal iontophoretic drug delivery: mechanistic analysis and application to polypeptide delivery. J. Pharm. Sci. 78: 370–375(1989).

    Google Scholar 

  9. Y. W. Chien, O. Siddiqui, W.-M. Shi, P. Lelawongs, and J.-C. Liu. Direct current iontophoretic transdermal delivery of peptide and protein drugs. J. Pharm. Sci. 78: 376–383(1989).

    Google Scholar 

  10. J. E. Riviere, N. A. Monteiro-Riviere, and A. O. Inman. Determination of lidocaine concentrations in skin after transdermal iontophoresis: effects of vasoactive drugs. Pharm. Res. 9: 211–214 (1992).

    Google Scholar 

  11. J. Singh, and M. Roberts. Transdermal delivery of drugs by iontophoresis: a review. Drug design and delivery. 4: 1–12 (1989).

    Google Scholar 

  12. E. Neumann. Membrane electroporation and direct gene transfer. Bioelectrochemistry and Bioenergetics. 28: 247–267(1992).

    Google Scholar 

  13. L. V. Chernomordik, and Y. A. Chizmadzhev In Electroporation and electrofusion in cell biology; E. Neumann, A. E. Sowers and C. A. Jordan, Ed.; Plenum: New York, 1989; pp 83–95.

    Google Scholar 

  14. K. Kinosita, M. Hibino, H. Itoh, M. Shigemori, K. Hirano, Y. Kirino, and T. Hayakawa In Guide to electroporation and electrofusion; D. C. Chang, B. M. Chassy, J. A. Saunders and A. E. Sowers, Ed.; Academic Press, Inc.: New York, 1992; pp 29–46.

    Google Scholar 

  15. L. V. Chernomordik, S. I. Sukharev, I. G. Abidor, and Y. A. Chizmadzhev. Breakdown of lipid bilayer membranes in an electric field. Biochim. et Biophys. Acta. 736: 203–213(1983).

    Google Scholar 

  16. D. C. Chang, and T. S. Reese. Changes in membrane structure induced by electroporation as revealed by rapid-freezing electron microscopy. Biophysics Journal. 58: 1–12(1990).

    Google Scholar 

  17. T. Y. Tsong. On electroporation of cell membranes and some related phemomena. Bioelectrochemistry and Bioenergetics. 24: 271–295(1990).

    Google Scholar 

  18. R. J. Scheuplein. Permeability of the skin: a review of major concepts. Curr. Probl. Dermatol. 7: 172–186(1978).

    Google Scholar 

  19. P. M. Elias. Plastic wrap revisited. Arch. Dermatol. 123: 1405–1406 (1987).

    Google Scholar 

  20. R. O. Potts, and R. H. Guy. Predicting Skin Permeability. Pharm. Res. 9: 663–669(1992).

    Google Scholar 

  21. I. H. Blank, and R. J. Scheuplein. Transport into and within the skin. Br. J. Derm. 81: 4–10(1969).

    Google Scholar 

  22. P. M. Elias. Epidermal barrier function: intercellular lamellar lipid structures, origin, composition and metabolism. J. Control. Rel. 15: 199–208(1991).

    Google Scholar 

  23. R. J. Scheuplein. Mechanism of percutaneous adsorption. I. Routes of penetration and the influence of solubility. J. Invest. Dermatol. 45: 334–346(1965).

    Google Scholar 

  24. P. Elias. Epidermal lipids, barrier function, and desquamation. JID 80: 44s–49s(1983).

    Google Scholar 

  25. D. Bommannan, L. Leung, J. Tamada, J. Sharifi, and R. Potts. Transdermal delivery of luteinizing hormone releasing hormone: comparison between electroporation and iontophoresis in vitro. Proceedings of International Symposium on Controlled Release of Bioactive Materials. 20: 97–98(1993).

    Google Scholar 

  26. M.-y. F. Lu, Lee, and G. S. Rao. Percutaneous absorption enhancement of leuprolide. Pharm. Res. 9: 1575–1579(1992).

    Google Scholar 

  27. L. Miller, C. Kolaskie, G. Smith, and J. Rivier. Transdermal iontophoresis of gonadotrophin releasing hormone (LHRH) and two analogues. J. Pharm. Sci. 79: 490–493(1990).

    Google Scholar 

  28. M. R. Prausnitz, V. G. 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 

  29. L. L. Wearley, and Y. W. Chien. Iontophoretic transdermal permeation of verapamil (III): Effect of binding and concentration gradient on reversibility of skin permeation rate. Int. J. Pharm. 59: 87–94(1990).

    Google Scholar 

  30. J. B. Phipps, and J. R. Gyory. Transdermal ion migration. Advanced drug delivery reviews. 9: 137–176(1992).

    Google Scholar 

  31. N. Monteiro-Riviere. Altered epidermal morphology secondary to lidocaine iontophoresis: in vivo and in vitro studies in porcine skin. Fundamental and Applied Toxicology. 15: 174–185(1990).

    Google Scholar 

  32. N. A. Monteiro-Riviere, A. O. Inman, and J. E. Riviere. Identification of the Pathway of Iontophoretic Drug Delivery: Light and Ultrastructural Studies Using Mercuric Chloride in Pigs. Pharm. Res. 11: 251–256 (1994).

    Google Scholar 

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Authors and Affiliations

  1. Cygnus Therapeutic Systems, Redwood City, California, 94063

    D. Bommi Bommannan, Janet Tamada, Lewis Leung & Russell O. Potts

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  1. D. Bommi Bommannan
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  2. Janet Tamada
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  3. Lewis Leung
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  4. Russell O. Potts
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Bommannan, D.B., Tamada, J., Leung, L. et al. Effect of Electroporation on Transdermal lontophoretic Delivery of Luteinizing Hormone Releasing Hormone (LHRH) in Vitro. Pharm Res 11, 1809–1814 (1994). https://doi.org/10.1023/A:1018983804635

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