title: Quantitative 3D molecular cutaneous absorption in human skin using label free nonlinear microscopy.
abstract: Understanding the penetration mechanisms of drugs into human skin is a key issue in pharmaceutical and cosmetics research. To date, the techniques available for percutaneous penetration of compounds fail to provide a quantitative 3D map of molecular concentration distribution in complex tissues as the detected microscopy images are an intricate combination of concentration distribution and laser beam attenuation upon deep penetration. Here we introduce and validate a novel framework for imaging and reconstructing molecular concentration within the depth of artificial and human skin samples. Our approach combines the use of deuterated molecular compounds together with coherent anti-Stokes Raman scattering spectroscopy and microscopy that permits targeted molecules to be unambiguously discriminated within skin layers. We demonstrate both intercellular and transcellular pathways for different active compounds, together with in-depth concentration profiles reflecting the detailed skin barrier architecture. This method provides an enabling platform for establishing functional activity of topically applied products.
authors.affiliation: Aix-Marseille Université, CNRS, Centrale Marseille, Institut Fresnel, UMR 7249, Domaine Universitaire de Saint Jérôme, F-13397 Marseille Cedex 20, France.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Chen
authors.affiliation: L'Oréal Recherche Avancée, 1 avenue Eugène Schueller, 93600 Aulnay-sous-bois, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Grégoire
authors.affiliation: L'Oréal Recherche Avancée, 1 avenue Eugène Schueller, 93600 Aulnay-sous-bois, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Formanek
authors.affiliation: L'Oréal Recherche Avancée, 1 avenue Eugène Schueller, 93600 Aulnay-sous-bois, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Galey
authors.affiliation: Aix-Marseille Université, CNRS, Centrale Marseille, Institut Fresnel, UMR 7249, Domaine Universitaire de Saint Jérôme, F-13397 Marseille Cedex 20, France. Electronic address: herve.rigneault@fresnel.fr.
authors.forename: Hervé
authors.initials: H
authors.lastname: Rigneault
mesh_terms: D002853:Chromatography, Liquid; D003517:Cyclopentanes / Q000494:pharmacology; D003879:Dermatologic Agents / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008853:Microscopy / Q000379:methods; D008875:Middle Aged; D054883:Oxylipins / Q000494:pharmacology; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013059:Spectrum Analysis, Raman; D053719:Tandem Mass Spectrometry
chemical_list: D003517:Cyclopentanes; D003879:Dermatologic Agents; D054883:Oxylipins; C000593049:tetrahydrojasmonic acid
keywords: Coherent anti-Stokes Raman scattering (CARS); Human skin; Molecular cutaneous absorption; Molecular penetration pathways; Quantitative molecular imaging