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      Follicular Penetration: Development of a Method to Block the Follicles Selectively against the Penetration of Topically Applied Substances

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          Abstract

          Investigations into the penetration pathways of topically applied substances through the skin play an important role in dermatological science. Recently, the hair follicles have increasingly been recognized as an important pathway for percutaneous penetration, although the role of the follicles has still not been clarified in detail. Therefore, the aim of the present study was to develop an in vivo method for the analysis of the follicular rate of penetration processes. In order to reach this goal, the follicles were excluded from the penetration process of topically applied substances. Different study designs were evaluated, and we were able to show that the application of nail varnish to each follicular orifice represents an effective method of blocking the follicles selectively against the penetration of topically applied substances. In dermatological science, there is new information on the physiology of skin penetration processes, thus allowing examination of the follicular rate of penetration and improvement of the pharmacokinetics of topically applied substances.

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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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            Penetration of Titanium Dioxide Microparticles in a Sunscreen Formulation into the Horny Layer and the Follicular Orifice

            Juergen Lademann, Hans-Juergen Weigmann, Christiane Rickmeyer … (1999)
            Coated titanium dioxide (TiO 2 ) microparticles are commonly used as UV filter substances in commercial sunscreen products. The penetration of these microparticles into the horny layer and the orifice of the hair follicle was investigated. The distribution of the microparticles in the horny layer was analyzed using the method of tape stripping in combination with spectroscopic measurements. Deeper layers of the stratum corneum were devoid of TiO 2 even after repetitive application of sunscreen preparation when analyzing interfollicular areas. Only in the areas of the pilosebaceous orifices could microparticles be identified. The penetration of TiO 2 was investigated in histological skin sections. A biopsy was taken from a skin area from which the horny layer had been removed by tape stripping. In isolated areas, a penetration of coated TiO 2 into the open part of the follicle was observed. The amount of TiO 2 found in a given follicle was less than 1% of the applied total amount of sunscreens. A penetration of microparticles into viable skin tissue could not be detected.
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              Penetration profile of microspheres in follicular targeting of terminal hair follicles.

              R Toll, U Jacobi, H. Richter … (2004)
              The transfollicular administration of pharmacologically active molecules is of current therapeutic interest, mainly with regard to delivery to specific sites of the hair follicle (HF) and the reduction of hepatic metabolism and systemic toxicity. HF are privileged pathways for specific molecules depending on formulations, which enter faster into these shunts than through the stratum corneum. The aim was to optimize the delivery of fluorescent microspheres into the HF, thereby, developing a standardized protocol for follicular targeting with microspheres. The number of HF showing penetration, as well as the depth of penetration, was determined. Freshly excised skin samples with terminal HF were divided into groups, with or without prior treatment with cyanoacrylate skin surface stripping-technique (CSSS). Thereafter microspheres at a size of 0.75-6.0 microm were applied according to the developed standardized protocol. Skin biopsies were obtained, shock-frozen, and sectioned in 5 microm slices. We demonstrated a selective penetration route of the microspheres into the HF. Optimal microsphere size proved to be approximately 1.5 microm, with a 55% rate of all HF, and with a maximum penetration depth of >2300 microm. Without previous CSSS treatment of the skin, the transfollicular microsphere penetration was below 27% with a maximum penetration depth of 1000 microm. Thus, the basis for follicular targeting of essential structures containing stem cells for keratinocytes, melanocytes, and mast cells has been laid.
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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
                ISSN (Print): 1660-5527
                ISSN (Electronic): 1660-5535
                Publication date Subscription-year: 2006
                Publication date (Print): July 2006
                Publication date (Electronic): 14 July 2006
                Volume: 19
                Issue: 4
                Pages: 216-223
                Affiliations
                Center for Experimental and Applied Cutaneous Physiology, Department of Dermatology, Medical Faculty Charité, Berlin, Germany
                Article
                Publisher ID: 93117 Other ID: Skin Pharmacol Appl Skin Physiol 2006;19:216–223
                DOI: 10.1159/000093117
                PubMed ID: 16679824
                SO-VID: 3c320505-ba11-41c9-9842-6f4cf5c08d7a
                Copyright © © 2006 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 : 23 May 2005
                Date accepted : 06 September 2005
                Page count
                Figures: 5, References: 38, Pages: 8
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Oncology & Radiotherapy,Pathology,Surgery,Dermatology,Pharmacology & Pharmaceutical medicine
                Keywords: Hair follicles,Tape stripping,UV/VIS spectrometer,Follicular penetration
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy, Pathology, Surgery, Dermatology, Pharmacology & Pharmaceutical medicine
                Keywords: Hair follicles, Tape stripping, UV/VIS spectrometer, Follicular penetration

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