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      Human Skin Penetration of Sunscreen Nanoparticles: In-vitro Assessment of a Novel Micronized Zinc Oxide Formulation

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          Abstract

          The extent to which topically applied solid nanoparticles can penetrate the stratum corneum and access the underlying viable epidermis and the rest of the body is a great potential safety concern. Therefore, human epidermal penetration of a novel, transparent, nanoparticulate zinc oxide sunscreen formulation was determined using Franz-type diffusion cells, 24-hour exposure and an electron microscopy to verify the location of nanoparticles in exposed membranes. Less than 0.03% of the applied zinc content penetrated the epidermis (not significantly more than the zinc detected in receptor phase following application of a placebo formulation). No particles could be detected in the lower stratum corneum or viable epidermis by electron microscopy, suggesting that minimal nanoparticle penetration occurs through the human epidermis.

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          Most cited references15

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          Skin penetration and distribution of polymeric nanoparticles.

          Encapsulation using nanoparticulate systems is an increasingly implemented strategy in drug targeting and delivery. Such systems have also been proposed for topical administration to enhance percutaneous transport into and across the skin barrier. However, the mechanism by which such particulate formulations facilitate skin transport remains ambiguous. In this study, confocal laser scanning microscopy (CLSM) was used to visualize the distribution of non-biodegradable, fluorescent, polystyrene nanoparticles (diameters 20 and 200 nm) across porcine skin. The surface images revealed that (i) polystyrene nanoparticles accumulated preferentially in the follicular openings, (ii) this distribution increased in a time-dependent manner, and (iii) the follicular localization was favoured by the smaller particle size. Apart from follicular uptake, localization of nanoparticles in skin "furrows" was apparent from the surface images. However, cross-sectional images revealed that these non-follicular structures did not offer an alternative penetration pathway for the polymer vectors, whose transport was clearly impeded by the stratum corneum.
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            Penetration of Titanium Dioxide Microparticles in a Sunscreen Formulation into the Horny Layer and the Follicular Orifice

            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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              Skin as a route of exposure and sensitization in chronic beryllium disease.

              Chronic beryllium disease is an occupational lung disease that begins as a cell-mediated immune response to beryllium. Although respiratory and engineering controls have significantly decreased occupational beryllium exposures over the last decade, the rate of beryllium sensitization has not declined. We hypothesized that skin exposure to beryllium particles would provide an alternative route for sensitization to this metal. We employed optical scanning laser confocal microscopy and size-selected fluorospheres to demonstrate that 0.5- and 1.0- micro m particles, in conjunction with motion, as at the wrist, penetrate the stratum corneum of human skin and reach the epidermis and, occasionally, the dermis. The cutaneous immune response to chemical sensitizers is initiated in the skin, matures in the local lymph node (LN), and releases hapten-specific T cells into the peripheral blood. Topical application of beryllium to C3H mice generated beryllium-specific sensitization that was documented by peripheral blood and LN beryllium lymphocyte proliferation tests (BeLPT) and by changes in LN T-cell activation markers, increased expression of CD44, and decreased CD62L. In a sensitization-challenge treatment paradigm, epicutaneous beryllium increased murine ear thickness following chemical challenge. These data are consistent with development of a hapten-specific, cell-mediated immune response following topical application of beryllium and suggest a mechanistic link between the persistent rate of beryllium worker sensitization and skin exposure to fine and ultrafine beryllium particles.
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                Author and article information

                Journal
                SPP
                Skin Pharmacol Physiol
                10.1159/issn.1660-5527
                Skin Pharmacology and Physiology
                S. Karger AG
                1660-5527
                1660-5535
                2007
                May 2007
                17 January 2007
                : 20
                : 3
                : 148-154
                Affiliations
                aTherapeutics Research Unit, Southern Clinical Division, Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, bAdvanced Nanotechnology Ltd, Welshpool, and cSchool of Biomedical Sciences, Curtin University of Technology, Bentley, Australia
                Article
                98701 Skin Pharmacol Appl Skin Physiol 2007;20:148–154
                10.1159/000098701
                17230054
                a6e02532-0a3b-4175-9ab3-9db440d8239a
                © 2007 S. Karger AG, Basel

                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
                : 08 August 2006
                : 21 November 2006
                Page count
                Figures: 3, Tables: 1, References: 24, Pages: 7
                Categories
                Original Paper

                Oncology & Radiotherapy,Pathology,Surgery,Dermatology,Pharmacology & Pharmaceutical medicine
                Transdermal delivery,Nanoparticle safety,Risk assessment

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