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Electroosmotic Pore Transport in Human Skin

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Abstract

Purpose. To determine the pathways and origin of electroosmotic flow in human skin.

Methods. Iontophoretic transport of acetaminophen in full thickness human cadaver skin was visualized and quantified by scanning electrochemical microscopy. Electroosmotic flow in the shunt pathways of full thickness skin was compared to flow in the pores of excised stratum corneum and a synthetic membrane pore. The penetration of rhodamine 6G into pore structures was investigated by laser scanning confocal microscopy.

Results. Electroosmotic transport is observed in shunt pathways in full thickness human skin (e.g., hair follicles and sweat glands), but not in pore openings of freestanding stratum corneum. Absolute values of the diffusive and iontophoretic pore fluxes of acetaminophen in full thickness human skin are also reported. Rhodamine 6G is observed to penetrate to significant depths (∼200 μm) along pore pathways.

Conclusions. Iontophoresis in human cadaver skin induces localized electroosmotic flow along pore shunt paths. Electroosmotic forces arise from the passage of current through negatively charged meso- or nanoscale pores (e.g., gap functions) within cellular regions that define the pore structure beneath the stratum corneum.

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REFERENCES

  1. M. J. Pikal. The role of electroosmotic flow in transdermal iontophoresis. Adv. Drug Deliv. Rev. 46:281-305 (2001).

    Google Scholar 

  2. A. Kim, P. G. Green, G. Rao, and R. H. Guy. Convective solvent flow across the skin during iontophoresis. Pharm. Res. 10:1315-1320 (1993).

    Google Scholar 

  3. D. Marro, Y. N. Kalia, M. B. Delgado-Charro, and R. H. Guy. Optimizing iontophoretic drug delivery: identification and distribution of the charge-carrying species. Pharm. Res. 18:1701-1708 (2001).

    Google Scholar 

  4. C. Curdy, Y. N. Kalia, and R. H. Guy. Post-iontophoresis recovery of human skin impedance in vivo. Eur. J. Pharm. Biopharm. 53:15-21 (2002).

    Google Scholar 

  5. C. Curdy, Y. N. Kalia, A. Naik, and R. H. Guy. Piroxicam delivery into human stratum corneum in vivo: iontophoresis versus passive diffusion. J. Control. Release 76:73-79 (2001).

    Google Scholar 

  6. S. Bose, W. R. Ravis, Y. J. Lin, L. Zhang, G. A. Hofmann, and A. K. Banga. Electrically-assisted transdermal delivery of buprienorphine. J. Control. Release 73:197-203 (2001).

    Google Scholar 

  7. S. K. Li, A. H. Ghanem, C. L. Teng, G. E. Hardee, and W. I. Higuchi. Iontophoretic transport of oligonucleotides across human epidermal membrane: a study of the Nernst-Planck model. J. Pharm. Sci. 90:915-931 (2001).

    Google Scholar 

  8. M. Kanebako, T. Inagi, and K. Takayama. Transdermal delivery of indomethacin by iontophoresis. Biol. Pharm. Bull. 25:779-782 (2002).

    Google Scholar 

  9. A. Luzardo-Alvarez, M. B. Delgado-Charro, and J. Blanco-Mendez. Iontophoretic delivery of ropinirole hydrochloride: effect of current density and vehicle formulation. Pharm. Res. 18:1714-1720 (2001).

    Google Scholar 

  10. R. M. Brand and C. Mueller. Transdermal penetration of atrazine, alachlor, and trifluralin: effect of formulation. Toxicol. Sci. 68:18-23 (2002).

    Google Scholar 

  11. M. J. Pikal and S. Shah. Transport mechanisms in iontophoresis. II. Electroosmotic flow and transference number measurements for hairless mouse skin. Pharm. Res. 7:213-221 (1990).

    Google Scholar 

  12. P. D. Grossman and J. C. Colburn. Capillary Electrophoresis. Theory and Practice, Academic Press Inc., New York, 1992

    Google Scholar 

  13. S. A. Miller, V. Y. Young, and C. R. Martin. Electroosmotic flow in template-prepared carbon nanotube membranes. J. Am. Chem. Soc. 123:12335-12342 (2001).

    Google Scholar 

  14. J. C. Giddings. Unified Separation Science, Wiley and Sons, New York, 1991.

    Google Scholar 

  15. H. Schaefer, A. Zesch, and G. Stuttgen. Skin Permeability, Springer-Verlag, New York, 1982.

    Google Scholar 

  16. E. R. Scott, H. S. White, and J. B. Phipps. Iontophoretic transport through porous membranes using scanning electrochemical microscopy: Application to in vitro studies of ion fluxes through skin. Anal. Chem. 65:1537-1545 (1993).

    Google Scholar 

  17. B. D. Bath, R. D. Lee, E. R. Scott, and H. S. White. Imaging molecular transport in porous membranes. Observation and analysis of electroosmotic flow in individual pores using the scanning electrochemical microscope. Anal. Chem. 70:1047-1058 (1998).

    Google Scholar 

  18. B. D. Bath, H. S. White, and E. R. Scott. Scanning electrochemical microscopy of iontophoretic transport in hairless mouse skin. Analysis of the relative contributions of diffusion, migration, and electroosmotic flow to transport in hair follicles. J. Pharm. Sci. 89:1537-1549 (2000).

    Google Scholar 

  19. E. R. Scott, J. B. Phipps, and H. S. White. Direct imaging of molecular transport through skin. J. Invest. Dermatol. 104:142-145 (1995).

    Google Scholar 

  20. G. Richard. Connexins: a connection with the skin. Exp. Dermatol. 9:77-96 (2000).

    Google Scholar 

  21. J. M. B. Anumonwo, S. M. Taffet, H. Gu, M. Chanson, A. P. Moreno, and M. Delmar. The carboxyl terminal domain regulates the unitary conductance and voltage dependence of connexin40 gap junction channels. Cir. Res. 88:666-673 (2001).

    Google Scholar 

  22. A. J. Bard and M. V. Mirkin. Scanning Electrochemical Microscopy, Marcel Dekker, New York, 2001.

    Google Scholar 

  23. G. L. Flynn, H. Durheim, and W. I. Higuchi. Permeation of hairless mouse skin II: membrane sectioning techniques and influence on alkanol permeabilities. J. Pharm. Sci. 70:52-56 (1981).

    Google Scholar 

  24. Y. Saito. A theoretical study on the diffusion current at the stationary electrodes of circular and narrow band types. Rev. Polarogr. 15:177-187 (1968).

    Google Scholar 

  25. N. G. Turner, L. Ferry, M. Price, C. Cullander, and R. H. Guy. Iontophoresis of Poly-L-lysines: The Role of Molecular Weight? Pharm. Res. 14:1322-1331 (1997).

    Google Scholar 

  26. H. L. Yeager. Transport Properties of Perfluorosulfonated Polymer Membranes. In H. L Yeager and A. Eisenberg (eds), Perfluorinated Ionomer Membranes, American Chemical Society, Washington DC, 1982, p. 41-64.

    Google Scholar 

  27. K. A. Mauritz, C. J. Hora, and A. J. Hopfinger. Ions in Polymers. In A. Eisenberg (ed), Advances in Chemistry Series, American Chemical Society, Washington, DC, 1980, pp. 123-144.

    Google Scholar 

  28. T. D. Gierke and W. Y. Hsu. The Cluster-Network Model of Ion Clustering in Perfluorosulfonated Membranes. In H. L. Yeager and A. Eisenberg (eds), Perfluorinated Ionomer Membranes, American Chemical Society, Washington, DC, 1982, pp. 283-307.

    Google Scholar 

  29. M. W. Verbrugge. Methanol diffusion in perfluorinated ion-exchange membranes. J. Electrochem. Soc. 136:417-423 (1989).

    Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry, University of Utah, Salt Lake City, Utah, 84112

    Olivia D. Uitto & Henry S. White

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  1. Olivia D. Uitto
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  2. Henry S. White
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Correspondence to Henry S. White.

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Uitto, O.D., White, H.S. Electroosmotic Pore Transport in Human Skin. Pharm Res 20, 646–652 (2003). https://doi.org/10.1023/A:1023259102279

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