title: Skin-mimetic chromatography for prediction of human percutaneous absorption of biologically active compounds occurring in medicinal plant extracts.
abstract: The main aim of this study was to predict quantitatively human percutaneous absorption of chosen compounds commonly occurring in plants which can be used as medicinal extracts in the drug and beauty industries. The most important human percutaneous descriptors, i.e. logKp(logarithm of the water/skin partition coefficient) and logJmax(logarithm of the maximum flux of solutes penetrating the skin), of fatty acids and polyphenols were determined using both in vitro and in silico methods. For in vitro determination of human percutaneous absorption, micellar liquid chromatography based on hexadecyltrimethylammonium bromide, sodium dodecyl sulfate and polyoxyethylene (23) lauryl ether (Brij35) was used. Human percutaneous absorption was characterized by entirely new QSAR/QRAR models based on retention, lipophilic, steric and electronic data as well as on the linear free energy relationship parameters. Many different correlations between human skin absorption and different physicochemical parameters were performed, e.g. the in silico estimated logKpvalue was correlated with the retention parameter logkw(logarithm of the retention factor extrapolated to pure water) from the systems imitating a cutaneous environment (R2= 0.92). Moreover, the influence of lipophilicity on percutaneous absorption was examined. The obtained correlation was excellent (R2= 0.95).
authors.affiliation: Department of Planar Chromatography, Chair of Physical Chemistry, Faculty of Chemistry, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Katarzyna
authors.identifier: http://orcid.org/0000-0002-9812-9114
authors.initials: K
authors.lastname: Stepnik
authors.affiliation: Department of Planar Chromatography, Chair of Physical Chemistry, Faculty of Chemistry, Maria Curie-Skłodowska University, Lublin, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Malinowska
mesh_terms: D000077286:Cetrimonium; D002593:Cetrimonium Compounds; D002853:Chromatography, Liquid / Q000379:methods*; D003198:Computer Simulation; D005227:Fatty Acids / Q000493:pharmacokinetics; D006801:Humans; D010936:Plant Extracts / Q000493:pharmacokinetics*; D010946:Plants, Medicinal / Q000737:chemistry*; D011092:Polyethylene Glycols; D059808:Polyphenols / Q000493:pharmacokinetics; D021281:Quantitative Structure-Activity Relationship; D012869:Skin Absorption / Q000187:drug effects*; D012967:Sodium Dodecyl Sulfate
chemical_list: D002593:Cetrimonium Compounds; D005227:Fatty Acids; D010936:Plant Extracts; D059808:Polyphenols; D012967:Sodium Dodecyl Sulfate; D011092:Polyethylene Glycols; C515901:Brij 35; D000077286:Cetrimonium
keywords: human percutaneous absorption; linear free energy relationship; medicinal plant extracts; micellar system; skin-mimetic chromatography