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Development of a percutaneous penetration predictive model with chromatographic and spectroscopic tools

Abstract : The stratum corneum (SC) is the upper skin layer and due to its particular composition, corneocytes embedded in a lipidic matrix, it owns a role of barrier function and protects our body against water loss, penetration of exogenous molecules and UV irradiation. Its lipidic matrix is composed of three major lipids: fatty acids, cholesterol and ceramides, organised in liquid crystalline phase. This high cohesion creates cement between corneocytes. This cement is the principal pathway taken by the exogenous molecules to penetrate the skin. Percutaneous penetration estimation of cosmetic products is today based on the Organisation for Economic Co-operation and Development (OECD) recommendations, regarding molecules structural characteristics i.e. Log Pow (polarity) and MW (molecular weight). The OECD claims that 100% dermal absorption may be assumed if the exogenous molecule molecular mass is lower than 500 g/mol and Log Pow ranged between -1 and +4. Besides these values, a 10% coefficient is applied. This approach is sometimes far from reality. Our work focused on developing new evaluation criteria of percutaneous penetration from three different approaches: affinity chromatography, fluorescence spectroscopy and FTIR microspectroscopy with a synchrotron source in order to modulate OECD predictions. Considering that skin barrier properties are closely linked to ceramide composition and conformation within the SC, two methods were developed to study the interaction between ceramides and exogenous molecules by affinity chromatography and fluorescence spectroscopy. A predictive criterion of percutaneous penetration was developed from each of these methods:  and I. The third methodology consisted of developing a predictive criterion, Sindex, by FTIR microspectroscopy with a synchrotron source, on microtomized cuts of human skin biopsies. A predictive cartography was build from Sindex. Our experimental design included exogenous molecules (e.g. UV filters, preservatives, cosmetic actives) with various Log Pow and MW (cf annexe 1). Molecules skin penetration was studied with a Franz cell device coupled to HPLC analysis. These results served as reference data to validate our predictive models and criteria.This work permitted to set up new methods for predicting skin penetration of exogenous molecules and to develop complementary predictive criterion to Log Pow and MW. These new criterion will serve to modulate OECD predictions.
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Elsa Jungman. Development of a percutaneous penetration predictive model with chromatographic and spectroscopic tools. Other. Université Paris Sud - Paris XI, 2012. English. ⟨NNT : 2012PA112226⟩. ⟨tel-00819391⟩

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