Modulation of the Barrier Function of the SkinHadgraft J.
Medway Sciences, NRI University of Greenwich, Chatham Maritime, UK
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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.
© 2001 S. Karger AG, Basel
- Albery WJ, Hadgraft J: Percutaneous absorption: In vivo experiments. J Pharm Pharmacol 1979;31:140–147.
- Potts RO, Francoeur ML: The influence of stratum corneum morphology on water permeability. J Invest Dermatol 1991;96:495–499.
- 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.
- Mitragotri S: In situ determination of partition and diffusion coefficients in the lipid bilayers of stratum corneum. Pharm Res 2000;17:1026–1029.
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.
- 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.
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.
- Bunge AL, Guy RH, Hadgraft J: The determination of a diffusional path length through the stratum corneum. Int J Pharm 1999;188:121–124.
- 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.
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.
- Liron Z, Cohen S: Percutaneous absorption of alkanoic acids. II. Application of regular solution theory. J Pharm Sci 1984;73:538–542.
Rosado CB: Formulation strategies in transdermal delivery; PhD thesis, University of Wales, 2000.
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.
- (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.
- 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.
- 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.
- 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.
- Hadgraft J, Valenta C: pH, pK(a) and dermal delivery. Int J Pharm 2000;200:243–247.
- 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.
- Alexander MY, Akhurst RJ: Liposome-mediated gene-transfer and expression via the skin. Hum Mol Genet 1995;4:2279–2285.
- 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.
- 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.
- 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.
- 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.
- Scheuplein RJ: Mechanism of percutaneous absorption. I. Routes of penetration and the influence of solubility. J Invest Dermatol 1965;45:334–346.
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