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oai:gupea.ub.gu.se:2077/278322013-04-23T12:44:09Zcom_2077_9527com_2077_4716com_2077_10556col_2077_9528col_2077_10557

Simonsson, Carl 2011-11-08T15:59:02Z 2011-11-08T15:59:02Z 2011-11-08 978-91-628-8384-3 http://hdl.handle.net/2077/27832 The skin is a remarkable barrier, protecting us from invasion of e.g. harmful microorganisms and UV-radiation. However, the skin is not adopted to resist repeated exposure to the multitude of xenobiotics introduced into modern society. Some of these chemicals are skin sensitizers, and exposure can lead to the development of contact allergy. Contact allergy has significant social and economic consequences, both for the individual and for society. It is therefore important to prevent sensitization. The skin also constitutes a potential route for administration of drugs, and much effort is put into the development of cutaneous and transdermal drug delivery systems. The work of this thesis aims to improve the understanding of processes related to the interactions between the skin and topically applied compounds, i.e. drugs and skin sensitizers. Specifically, two-photon microscopy has been used to study the cutaneous absorption and distribution of model drugs and a series of model skin sensitizers. Improved cutaneous absorption was demonstrated using formulations composed of lipid cubic phases. The work also showed elevated sensitization potency of haptens depending on delivery vehicles. Putative mechanistic explanations for the observed effects have been proposed. Specifically, phthalates were shown to increase the sensitization potency of isothiocyanates. The phthalate-induced effect could be linked to a PSU-targeted delivery of the haptens into the skin. It could also be shown that vehicles alter hapten reactivity to stratum corneum proteins leading to variations in sensitization potency. Moreover, hapten protein targets in skin have been identified using caged fluorescent model hapten. Specifically, basal cell keratinocytes and the keratins were identified as specific hapten targets in the skin. In conclusion, the work presented in this thesis contributes to the general understanding of the mechanisms involved in the cutaneous absorption of topically applied drugs and skin sensitizers. It also demonstrates the capabilities of using TPM when investigating the interactions between the skin and xenobiotics. eng Lipid cubic phases in topical drug delivery: Visualization of skin distribution using two-photon microscopy. Bender, J., Simonsson, C., Smedh, M., Engström, S., and Ericson, M.B., Journal of Controlled Release, 2008. 129: 163-169. ::doi::10.1016/j.jconrel.2008.04.020 Accumulation of FITC near stratum corneum-visualizing epidermal distribution of a strong sensitizer using two-photon microscopy. Samuelsson, K., Simonsson, C., Jonsson, C.A., Westman, G., Ericson, M.B., and Karlberg, A.T., Contact Dermatitis, 2009. 61: 91-100. ::doi::10.1111/j.1600-0536.2009.01591.x A study of the enhanced sensitizing capacity of a contact allergen in lipid vesicle formulations. Simonsson, C., Madsen, J.T., Graneli, A., Andersen, K.E., Karlberg, A.-T., Jonsson, C.A., and Ericson, M.B., Toxicology and Applied Pharmacology, 2011. 252: 221-227. ::doi::10.1016/j.taap.2011.02.010 Caged fluorescent haptens reveal the generation of cryptic epitopes in allergic contact dermatitis. Simonsson, C., Andersson, S.I., Stenfeldt, A.L., Bergström, J., Bauer, B., Jonsson, C.A., Ericson, M.B., and Broo, K.S., Journal of Investigative Dermatology, 2011. 131: 1486-1493. ::doi::10.1038/jid.2010.422 The pilosebaceous unit – a phthalate-induced highway to skin sensitization. Simonsson, C., Stenfeldt, A.L., Karlberg, A.-T., Ericson, M.B., Jonsson, C.A Submitted for publication contact allergy cubic phases cutaneous absorption bromobimane isothiocyanate lipid vesicles nano pilosebaceous unit , two-photon microscopy New insights in contact allergy and drug delivery. A study of formulation effects and hapten targets in skin using two-photon fluorescence microscopy Text Doctoral thesis Doctor of Philosophy carl.simonsson@chem.gu.se University of Gothenburg. Faculty of Science Department of Chemistry ; Institutionen för kemi Fredagen den 25 november 2011, kl 09:15, sal KB, Institutionen för Kemi, Kemigården 4, Göteborg 2011-11-25 MNF open.access