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A Novel in Vitro Percutaneous Penetration Model: Evaluation of Barrier Properties with P-Aminobenzoic Acid and Two of Its Derivatives

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Purpose

The objective of this study was to evaluate the utility of a stratum corneum substitute (SCS) as a novel in vitro percutaneous penetration model. The SCS consists of synthetic stratum corneum (SC) lipids (cholesterol, free fatty acids, and specific ceramides) applied onto a porous substrate. The composition, organization, and orientation of lipids in the SCS bear high resemblance to that of the intercellular barrier lipids in SC.

Methods

The barrier integrity of the SCS was evaluated by means of passive diffusion studies, using three model compounds with different lipophilicities. The effects of lipid layer thickness, permeant lipophilicity, and altered lipid composition on the barrier properties were investigated, using isolated human SC as a control sample.

Results

For all three model compounds, the permeability characteristics of the SCS with a 12-μm-thick lipid layer closely resemble those of human SC. Modification of the lipid composition, generating an SCS that lacks the characteristic long periodicity phase as present in SC, was accompanied by a 2-fold increased permeability.

Conclusions

The SCS offers an attractive tool to predict solute permeation through human skin. Moreover, as its lipid composition can be modified, they may also serve as a suitable screening model for diseased skin.

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Acknowledgments

This work was supported by a grant from the Technology Foundation STW (LGN4654). The authors would like to thank the Center for Electron Microscopy (Leiden University Medical Center) and the Department of Plant Sciences (Wageningen University) for the use of their electron microscopy facilities.

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Authors and Affiliations

  1. Department of Drug Delivery Technology, Leiden/Amsterdam Center for Drug Research, University of Leiden, PO Box 9052, 2300 RA, Leiden, The Netherlands

    Miranda de Jager, Wouter Groenink, Nadezhda Angelova & Joke Bouwstra

  2. Department of Physico-Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain

    Ruth Bielsa i Guivernau

  3. Department of Pharmacy, University of Uppsala, Uppsala, Sweden

    Elin Andersson

  4. Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands

    Maria Ponec

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  1. Miranda de Jager
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  2. Wouter Groenink
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  3. Ruth Bielsa i Guivernau
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  5. Nadezhda Angelova
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  7. Joke Bouwstra
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Correspondence to Joke Bouwstra.

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de Jager, M., Groenink, W., Bielsa i Guivernau, R. et al. A Novel in Vitro Percutaneous Penetration Model: Evaluation of Barrier Properties with P-Aminobenzoic Acid and Two of Its Derivatives. Pharm Res 23, 951–960 (2006). https://doi.org/10.1007/s11095-006-9909-1

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  • DOI: https://doi.org/10.1007/s11095-006-9909-1

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