Skip to main content
SpringerLink
Log in

Alteration of electroosmotic volume flow through skin by polyethylene glycols

  • Research Article
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

We have studied the effect of polyethylene glycols (PEGs) on the iontophoretic flux of acetaminophen (AAP) using conventional in vitro iontophoresis methodology. A series of PEGs with average molecular weight (MW) ranging from about 100 to 1,500 was studied. The results were analyzed to explain how PEGs affect the electroosmosis and flux through skin. As a marker molecule for the direction and magnitude of electroosmotic volume flow (EVF), AAP was used. PEG decreased both anodal and cathodal AAP flux markedly. The magnitude of this decrease in flux increased as the MW and the concentration of PEG increased. From the Helmholtz–Smoluchowski equation, it was expected that the increase in viscosity and the decrease in dielectric constant are thought to be the main reason for the decrease in EVF and the flux. The large increase in solubility of AAP in PEG solution may also play an important role, because this increase lowers the partition of AAP into the stratum corneum. When 30 % diethylene glycol solution was used, the magnitude of EVF was estimated to be about 1.5 μl/cm2 h, and it decreased as the MW of the PEG increased. These results and discussions clearly suggest that the incorporation of organic solubilizers and penetration enhancers into the iontophoretic formulation should be carefully decided after a thorough understanding of their effect on flux. Overall, these results provide further mechanistic insights into the role of electroosmosis in flux through skin, and how they can be modulated by PEG and their MW.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Arnold, K., A. Herrmann, L. Pratsch, and K. Gawrisch. 1985. The dielectric properties of aqueous solutions of poly(ethylene glycol) and their influence on membrane structure. Biochimica et Biophysica Acta 815(3): 515–518.

    Article  CAS  PubMed  Google Scholar 

  • Barry, B.W. 2001. Novel mechanisms and devices to enable successful transdermal drug delivery. European Journal of Pharmaceutical Science 14(2): 101–114.

    Article  CAS  Google Scholar 

  • Cheng, G., X. Fan, W. Tian, Y. Liu, and G. Liu. 2010. Study on anionic polymerization of ethylene oxide initiated by ammonium/triisobutylaluminum. Journal of Polymer Research 17: 529–534.

    Article  CAS  Google Scholar 

  • Cevc, G. 2004. Lipid vesicles and other colloids as drug carriers on the skin. Advanced Drug Delivery Reviews 56(5): 675–711.

    Article  CAS  PubMed  Google Scholar 

  • Chessa, M., C. Caddeo, D. Valenti, M. Manconi, C. Sinico, and A.M. Fadda. 2011. Effect of penetration enhancer containing vesicles on the percutaneous delivery of quercetin through new born pig skin. Pharmaceutics 3: 497–509.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chesnoy, S., D. Durand, J. Doucet, and G. Couarraze. 1999. Structural parameters involved in the permeation of propranolol HCl by iontophoresis and enhancers. Journal of Controlled Release 58(2): 163–175.

    Article  CAS  PubMed  Google Scholar 

  • Fruijtier-Pölloth, C. 2005. Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products. Toxicology 214(1–2): 1–38.

    Article  PubMed  Google Scholar 

  • Gibson, L.E., and R.E. Cooke. 1959. A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Pediatrics 23: 545–549.

    CAS  PubMed  Google Scholar 

  • Gratieri, T., and Y.N. Kalia. 2013. Mathematical models to describe iontophoretic transport in vitro and in vivo and the effect of current application on the skin barrier. Advanced Drug Delivery Reviews 65: 315–329.

    Article  CAS  PubMed  Google Scholar 

  • Guy, R.H., and J. Hadgraft. 1988. Physicochemical aspects of percutaneous penetration and its enhancement. Pharmaceutical Research 5: 753–758.

    Article  CAS  PubMed  Google Scholar 

  • Guy, R.H., Y.N. Kalia, M.B. Delgado-Charro, V. Merino, A. Lopez, and D. Marro. 2000. Iontophoresis: Electrorepulsion and electroosmosis. Journal of Controlled Release 64: 129–132.

    Article  CAS  PubMed  Google Scholar 

  • Hirvonen, J., Y.N. Kalia, and R.H. Guy. 1996. Transdermal delivery of peptides by iontophoresis. Nature Biotechnology 14: 1710–1713.

    Article  CAS  PubMed  Google Scholar 

  • Hirvonen, J., and R.H. Guy. 1997. Iontophoretic delivery across the skin: Electroosmosis and its modulation by drug substances. Pharmaceutical Research 14: 1258–1263.

    Article  CAS  PubMed  Google Scholar 

  • Hirvonen, J., and R.H. Guy. 1998. Transdermal iontophoresis: Modulation of electroosmosis by polypeptide. Journal of Controlled Release 50(1–3): 283–289.

    Article  PubMed  Google Scholar 

  • Jain, A., and S.K. Jain. 2008. PEGylation: An approach for drug delivery. A review. Critical Reviews in Therapeutic Drug Carrier Systems 25(5): 403–447.

    Article  CAS  PubMed  Google Scholar 

  • Khan, A., M. Yasir, M. Asif, I. Chauhan, A.P. Singh, R. Sharma, P. Singh, and S. Rai. 2011. Iontophoretic drug delivery: History and application. Journal of Applied Pharmaceutical Science 01(03): 11–24.

    Google Scholar 

  • Kim, A., P.G. Green, G. Rao, and R.H. Guy. 1993. Convective solvent flow across the skin during iontophoresis. Pharmaceutical Research 10: 1315–1320.

    Article  CAS  PubMed  Google Scholar 

  • Knop, K., R. Hoogenboom, D. Fischer, and U.S. Schubert. 2010. Poly(ethylene glycol) in drug delivery: Pros and cons as well as potential alternatives. Angewandte Chemie International Edition 49: 6288–6308.

    Article  CAS  Google Scholar 

  • Lee, J.H., and S.Y. Oh. 2005. Current pretreatment of skin and its effect on the permeability. Journal of Pharmaceutical Investigation 35(2): 81–87.

    Article  CAS  Google Scholar 

  • Lee, S.Y., N.Y. Jeong, and S.Y. Oh. 2014. Modulation of electroosmosis and flux through skin: Effect of propylene glycol. Archives of Pharmacal Research 37(4): 484–493.

    Article  CAS  PubMed  Google Scholar 

  • Malmberg, C.G., and A.A. Maryott. 1956. Dielectric constant of water from 0° to 100 °C. Journal of Research of the National Bureau of Standards 56(1): 1–8.

    Article  CAS  Google Scholar 

  • Marro, D., R.H. Guy, and M.B. Delgado-Charro. 2001a. Characterization of the iontophoretic permselectivity properties of human and pig skin. Journal of Controlled Release 70: 213–217.

    Article  CAS  PubMed  Google Scholar 

  • Marro, D., Y.N. Kalia, M.B. Delgado-Charro, and R.H. Guy. 2001b. Contributions of electromigration and electroosmosis to iontophoretic drug delivery. Pharmaceutical Research 18(12): 1701–1708.

    Article  CAS  PubMed  Google Scholar 

  • Mitragotri, S. 2000. Synergistic effect of enhancers for transdermal drug delivery. Pharmaceutical Research 17(11): 1354–1359.

    Article  CAS  PubMed  Google Scholar 

  • Ngawhirunpat, T., N. Worachun, P. Opanasopit, T. Rojanarata, and S. Panomsuk. 2013. Cremophor RH40-PEG 400 microemulsions as transdermal drug delivery carrier for ketoprofen. Pharmaceutical Development and Technology 18(4): 798–803.

    Article  CAS  PubMed  Google Scholar 

  • Oehme, F. 1962. Dielektrische Messmethoden zur quantitativen Analyse und für chemische Strukturbestimmungen. Weinheim: Verlag Chemie.

    Google Scholar 

  • Oh, S.Y., and R.H. Guy. 1995. Effect of iontophoresis on the electrical properties of human skin in vivo. International Journal of Pharmaceutics 124: 137–142.

    Article  CAS  Google Scholar 

  • Pamukcu, S., and J.K. Wittle. 1992. Electrokinetic removal of selected heavy metals from soil. Environmental Progress 11(3): 241–250.

    Article  CAS  Google Scholar 

  • Pasut, G., M. Sergi, and F.M. Veronese. 2008. Anti-cancer PEG-enzymes: 30 years old, but still a current approach. Advanced Drug Delivery Reviews 60(1): 69–78.

    Article  CAS  PubMed  Google Scholar 

  • Pikal, M.J. 2001. The role of electroosmotic flow in transdermal iontophoresis. Advanced Drug Delivery Reviews 46(1–3): 281–305.

    Article  CAS  PubMed  Google Scholar 

  • Prausnitz, M.R., S. Mitragotri, and R. Langer. 2004. Current status and future potential of transdermal drug delivery. Nature Reviews Drug Discovery 3: 115–124.

    Article  CAS  PubMed  Google Scholar 

  • Prausnitz, M.R., and R. Langer. 2008. Transdermal drug delivery. Nature Biotechnology 26(11): 1261–1268.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schoellhammer, C.M., D. Blankschtein, and R. Langer. 2014. Skin permeabilization for transdermal drug delivery: Recent advances and future prospects. Expert Opinion Drug Delivery 11(3): 393–407.

    Article  CAS  Google Scholar 

  • Shin, S.C., and H.J. Lee. 2002. Controlled release of triprolidine using ethylenevinyl acetate membrane and matrix systems. European Journal of Pharmaceutics and Biopharmaceutics 54(2): 201–206.

    Article  CAS  PubMed  Google Scholar 

  • Shingade, G.M., A. Quazi, P.M. Sabale, N.D. Grampurohit, M.V. Gadhave, S.L. Jadhav, D.D. Gaikwad, and K.T. Patil. 2012. Review on: Recent trend on transdermal drug delivery system. Journal of Drug Delivery & Therapeutics 2(1): 66–75.

    CAS  Google Scholar 

  • Sieg, A., R.H. Guy, and M.B. Delgado-Charro. 2004. Noninvasive glucose monitoring by reverse iontophoresis in vivo: Application of the internal standard concept. Clinical Chemistry 50(8): 1383–1390.

    Article  CAS  PubMed  Google Scholar 

  • Sloan, J.B., and K. Soltani. 1986. Iontophoresis in dermatology. Journal of the American Academy of Dermatology 5: 671–684.

    Article  Google Scholar 

  • Srinivasan, V., W.I. Higuchi, S.M. Sims, A.H. Ghanem, and C.R. Behl. 1989. Transdermal iontophoretic drug delivery: Mechanistic analysis and application to polypeptide delivery. Journal of Pharmaceutical Science 78: 370–375.

    Article  CAS  Google Scholar 

  • Thomas, B.J., and B.C. Finnin. 2004. The transdermal revolution. Drug Discovery Today 9(16): 697–703.

    Article  CAS  PubMed  Google Scholar 

  • Tokumoto, S., K. Mori, N. Higo, and K. Sugibayashi. 2005. Effect of electroporation on the electroosmosis across hairless mouse skin in vitro. Journal of Controlled Release 105: 296–304.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This Research was supported by the Sookmyung Women’s University Research Grants 2013.

Author information

Authors and Affiliations

  1. College of Pharmacy, Sookmyung Women’s University, Seoul, 140-742, Korea

    Seung Yeon Lee & Seaung Youl Oh

Authors
  1. Seung Yeon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seaung Youl Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seaung Youl Oh.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, S.Y., Oh, S.Y. Alteration of electroosmotic volume flow through skin by polyethylene glycols. Arch. Pharm. Res. 38, 1397–1405 (2015). https://doi.org/10.1007/s12272-014-0504-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-014-0504-4

Keywords

Search

Navigation