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      Which Skin Model Is the Most Appropriate for the Investigation of Topically Applied Substances into the Hair Follicles?

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          Abstract

          It has recently been demonstrated by the utilization of different techniques, such as differential stripping and laser scanning microscopy, that the hair follicles represent an efficient long-term reservoir for topically applied substances. In the present paper, the different in vivo techniques are compared to those of in vitro analysis. It was found that in vitro measurements on pig ear skin are highly superior for the analysis of follicular penetration, as compared to in vitro investigations on excised human skin, mainly due to the fact that the human skin contracts after removal. Restretching of the skin to its original size mainly stretches the interfollicular fibres, whereas the fibres around the hair follicles remain contracted. In contrast to excised human skin, pig ear tissue does not contract when the cartilage is not removed. Moreover, it has an intact barrier on both sides of the ear. Regardless of the fact that the hair follicles on pig ear skin are larger than those of humans, the porcine ear skin represents a more suitable in vitro model for the analysis of the penetration and storage of topically applied substances in the hair follicles than excised human skin.

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          Porcine ear skin: an in vitro model for human skin.

          Ute Jacobi, Marco Kaiser, Rani Toll … (2007)
          Porcine ear skin is used in studies of percutaneous penetration as a substitute for human skin. The structure of this tissue, including hair follicles, was studied qualitatively and quantitatively in comparison with human skin. Sections of shock-frozen biopsies, biopsies embedded in paraffin and cyanoacrylate skin surface biopsies were investigated using microscopy. The thickness of the different skin layers and the follicular characteristics were determined. The thickness of the stratum corneum was 17-28 microm, whereas the viable epidermis was 60-85 microm thick. On 1 cm(2), 11-25 hairs were detected, showing a diameter of 58-97 microm and a maximal extension depth of 0.96-1.38 mm into the skin. The orifices of the porcine infundibula showed a diameter of approximately 200 microm. The results obtained are similar to those of human skin, indicating the suitability of this porcine tissue as a model for human skin.
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            Comparison of human skin or epidermis models with human and animal skin in in-vitro percutaneous absorption.

            Fritz P. Schmook, Josef Meingassner, Andreas Billich (2001)
            For the study of in-vitro skin penetration of candidate drugs, excised animal skin is frequently used as a replacement for human skin. Reconstructed human skin or epidermis equivalents have been proposed as alternatives. We compared the penetration properties of human, pig and rat skin with the Graftskin LSE (living skin equivalent) and the Skinethic HRE (human reconstructed epidermis) models using four topical dermatological drugs (salicylic acid, hydrocortisone, clotrimazole and terbinafine) with widely varying polarity. In agreement with published data, pig skin appeared as the most suitable model for human skin: the fluxes through the skin and concentrations in the skin were of the same order of magnitude for both tissues, with differences of at most two- or fourfold, respectively. Graftskin LSE provided an adequate barrier to salicylic acid, but was very permeable for the more hydrophobic compounds (e.g. about 900-fold higher flux and 50-fold higher skin concentrations of clotrimazole as compared to human skin), even more than rat skin. In the case of the Skinethic HRE, we found similar concentrations of salicylic acid as in human skin and an approximately sevenfold higher flux. In contrast, the permeation of hydrophobic compounds through the epidermal layer was vastly higher than through split-thickness human skin (up to a factor of about 800). To conclude, currently available reconstituted skin models cannot be regarded as generally useful for in-vitro penetration studies.
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              The Pig as an Experimental Animal Model of Percutaneous Permeation in Man: Qualitative and Quantitative Observations – An Overview

              Gad Simon, Howard Maibach (2000)
              The pig has been a well-recognized experimental animal in biomedical research for many centuries. Physiological and anatomical similarities between man and pig made this animal a good model for man in many research areas. Pharmacological and toxicological research on the skin is often based on knowledge of skin absorption and percutaneous permeation. Anatomical, physiological and biochemical similarities are cited and various uses of the pig as a model for man in the investigation of skin permeation are reviewed. Further, several isolated organ models are reviewed. The importance of full details of the experimental animal, namely its age, sex, breed, size (weight) and body region, is emphasized.
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                Author and article information

                Journal
                Journal ID (publisher-id): SPP
                Journal ID (nlm-ta): Skin Pharmacol Physiol
                Journal ID (doi): 10.1159/issn.1660-5527
                Title: Skin Pharmacology and Physiology
                Publisher: S. Karger AG
                ISBN: 978-3-8055-9378-6
                ISBN: 978-3-8055-9379-3
                ISSN (Print): 1660-5527
                ISSN (Electronic): 1660-5535
                Publication date Subscription-year: 2010
                Publication date (Print): January 2010
                Publication date (Electronic): 14 January 2010
                Volume: 23
                Issue: 1
                Pages: 47-52
                Affiliations
                Center of Experimental and Applied Cutaneous Physiology (CCP), Department of Dermatology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany
                Article
                Publisher ID: 257263 Other ID: Skin Pharmacol Physiol 2010;23:47–52
                DOI: 10.1159/000257263
                PubMed ID: 20090408
                SO-VID: d837a86c-b27c-4d90-9404-10a89256f1af
                Copyright © © 2010 S. Karger AG, Basel
                License:

                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. 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 government 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.

                History
                Date received : 30 July 2009
                Date accepted : 03 September 2009
                Page count
                Figures: 4, References: 39, Pages: 6
                Categories
                Subject: Paper

                ScienceOpen disciplines: Oncology & Radiotherapy,Pathology,Surgery,Dermatology,Pharmacology & Pharmaceutical medicine
                Keywords: Excised human skin,Porcine ear skin,Follicular penetration
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy, Pathology, Surgery, Dermatology, Pharmacology & Pharmaceutical medicine
                Keywords: Excised human skin, Porcine ear skin, Follicular penetration

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