title: In silico and in vitro filters for the fast estimation of skin permeation and distribution of new chemical entities.
abstract: The development of in silico and in vitro tools to estimate or predict the passive human skin permeation and distribution of new chemical entities, useful in dermal drug delivery, in absorption studies of toxic compounds, and in the cosmetics industry, is presented. In vitro permeation parameters were measured using the artificial membrane PAMPA-skin. The Volsurf approach was then applied to extract pertinent descriptors from molecular interaction fields characterizing the molecular structure of tested compounds. Two useful three-dimensional solvatochromic models able to predict PAMPA permeation parameters directly from the molecular structure were obtained using the partial least squares analysis. The models also provide valuable information to understand the link between physicochemical and structural properties of tested compounds and their interactions with the artificial membrane PAMPA-skin and can be useful to rapidly estimate their permeation through the human skin.
authors.affiliation: LCT-Pharmacochimie, Section des sciences pharmaceutiques, Université de Genève, Université de Lausanne, Quai Ernest-Ansermet 30, CH-1211, Genève 4, Suisse.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ottaviani
authors.forename: Sophie
authors.initials: S
authors.lastname: Martel
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Carrupt
mesh_terms: D006801:Humans; D008567:Membranes, Artificial; D008954:Models, Biological; D008958:Models, Molecular; D000442:Octanols; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D012869:Skin Absorption; D014867:Water
chemical_list: D008567:Membranes, Artificial; D000442:Octanols; D004364:Pharmaceutical Preparations; D014867:Water