Journal Mobile Options
Table of Contents
Vol. 14, Suppl. 1, 2001
Issue release date: August 2001

Modulation of the Barrier Function of the Skin

Hadgraft J.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Transport of xenobiotics across the stratum corneum, the rate-controlling membrane of skin, is slow and the mechanism appears complex. However, the basic transfer is controlled by fundamental physicochemical concepts, the predominant of which are partition (K), diffusion (D) and solubility (Cs). In order to change the rate of penetration it is therefore clear that it is these parameters that should be targeted. In most instances enhancement strategies are adopted to improve D, K or Cs, however there are instances in which permeation reduction may be beneficial. Examples include the topical application of sunscreens or insect repellents. This publication demonstrates the way in which modulation effects can be assessed and the difficulties involved in determining which of the physicochemical parameter(s) are being affected. If the formulation influences more than one, synergism can often be seen. Advances in computer modelling have provided an insight into the mechanisms of action of some of the chemical enhancers at a molecular level. Enhanced skin absorption has been reported for the delivery of macromolecules such as insulin (associated with transfersomes) or DNA (as a DOTAP complex). The barrier property of the skin must be modulated for this to be achieved. However the precise mechanisms of action have not been elucidated.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Albery WJ, Hadgraft J: Percutaneous absorption: In vivo experiments. J Pharm Pharmacol 1979;31:140–147.

    External Resources

  2. Potts RO, Francoeur ML: The influence of stratum corneum morphology on water permeability. J Invest Dermatol 1991;96:495–499.
  3. Gay CL, Murphy TM, Hadgraft J, Kellaway IW, Evans JC, Rowlands CC: An electron spin resonance study of skin penetration enhancers. Int J Pharm 1989;49:39–45.

    External Resources

  4. Mitragotri S: In situ determination of partition and diffusion coefficients in the lipid bilayers of stratum corneum. Pharm Res 2000;17:1026–1029.

    External Resources

  5. Pellett MA, Watkinson AC, Hadgraft J, Brain KR: Comparison of permeability data from traditional diffusion cells and ATR-FTIR spectroscopy. 1. Synthetic membranes. Int J Pharm 1997;154:205–215.
  6. Harrison JE, Watkinson AC, Green DM, Hadgraft J, Brain K: The relative effect of Azone and Transcutol on permeant diffusivity and solubility in human stratum corneum. Pharm Res 1996;13:542–546.
  7. Pellett MA, Watkinson AC, Hadgraft J, Brain KR: Comparison of permeability data from traditional diffusion cells and ATR-FTIR spectroscopy. 2. Determination of diffusional path lengths in synthetic membranes and human stratum corneum. Int J Pharm 1997;154:217–227.
  8. Bunge AL, Guy RH, Hadgraft J: The determination of a diffusional path length through the stratum corneum. Int J Pharm 1999;188:121–124.
  9. Ongpipattanakul B, Burnette RR, Potts RO, Francoeur ML: Evidence that oleic acid exists in a separate phase within stratum corneum lipids. Pharm Res 1991;8:350–354.
  10. Hadgraft J, Peck J, Williams DG, Pugh WJ, Allan G: Mechanisms of action of skin penetration enhancers retarders: Azone and analogues. Int J Pharm 1996;141:17–25.
  11. Liron Z, Cohen S: Percutaneous absorption of alkanoic acids. II. Application of regular solution theory. J Pharm Sci 1984;73:538–542.

    External Resources

  12. Rosado CB: Formulation strategies in transdermal delivery; PhD thesis, University of Wales, 2000.
  13. Cross SE, Pugh J, Hadgraft J, Roberts MS: Probing the effect of vehicles on topical delivery: Understanding the basic relationship between solvent and solute penetration kinetics using silicone membranes. Pharm Res, in press.
  14. (a) Dias MM: Facilitated percutaneous penetration; PhD thesis, University of Wales, 2001.14 (b) Lafforgue C, Eynard I, Falson F, Watkinson AC, Hadgraft J: Percutaneous absorption of methyl nicotinate. Int J Pharm 1995;121:89–93.

    External Resources

  15. Bommannan D, Potts RO, Guy RH: Examination of the effect of ethanol on human stratum corneum in vivo using infrared spectroscopy. J Control Release 1991;16:299–304.
  16. Amdidouche D, Montassier P, Poelman MC, Duchene D: Evaluation by laser-Doppler velocimetry of the attenuation of tretinoin induced skin irritation by beta-cyclodextrin complexation. Int J Pharm 1994;111:111–116.

    External Resources

  17. Iervolino M, Cappello B, Raghavan SL, Hadgraft, J: Penetration enhancement of ibuprofen from supersaturated solutions through human skin. Int J Pharm 2001;212:131–141.

    External Resources

  18. Hadgraft J, Valenta C: pH, pK(a) and dermal delivery. Int J Pharm 2000;200:243–247.
  19. Valenta C, Cladera J, O’Shea P, Hadgraft J: Effect of phloretin on the percutaneous absorption of lignocaine across human skin. J Pharm Sci 2001;90:485–492.
  20. Alexander MY, Akhurst RJ: Liposome-mediated gene-transfer and expression via the skin. Hum Mol Genet 1995;4:2279–2285.
  21. Birchall JC, Marichal C, Campbell L, Alwan A, Hadgraft J, Gumbleton M: Gene expression in an intact ex-vivo skin tissue model following percutaneous delivery of cationic liposome-plasmid DNA complexes. Int J Pharm 2000;197:233–238.

    External Resources

  22. Niemiec SM, Ramachandran C, Weiner N: Influence of nonionic liposomal composition on topical delivery of peptide drugs into pilosebaceous units: An in vivo study using the hamster ear model. Pharm Res 1995;12:1184–1188.
  23. Rolland A, Wagner N, Chatelus A, Shroot B, Schaefer H: Site-specific drug delivery to pilosebaceous structures using polymeric microspheres. Pharm Res 1993;10:1738–1744.
  24. Cevc G, Schatzlein A, Blume G: Transdermal drug carriers: Basic properties, optimization and transfer efficiency in the case of epicutaneously applied peptides. J Control Release 1995;36:3–16.

    External Resources

  25. Scheuplein RJ: Mechanism of percutaneous absorption. I. Routes of penetration and the influence of solubility. J Invest Dermatol 1965;45:334–346.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50