title: Vehicle effects on human stratum corneum absorption and skin penetration.
abstract: This study evaluated the effects of three vehicles-ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)-on stratum corneum (SC) absorption and diffusion of the [14C]-model compounds benzoic acid and butenafine hydrochloride to better understand the transport pathways of chemicals passing through and resident in SC. Following application of topical formulations to human dermatomed skin for 30 min, penetration flux was observed for 24 h post dosing, using an in vitro flow-through skin diffusion system. Skin absorption and penetration was compared to the chemical-SC (intact, delipidized, or SC lipid film) binding levels. A significant vehicle effect was observed for chemical skin penetration and SC absorption. IPA resulted in the greatest levels of intact SC/SC lipid absorption, skin penetration, and total skin absorption/penetration of benzoic acid, followed by IPM and EtOH, respectively. For intact SC absorption and total skin absorption/penetration of butenafine, the vehicle that demonstrated the highest level of sorption/penetration was EtOH, followed by IPA and IPM, respectively. The percent doses of butenafine that were absorbed in SC lipid film and penetrated through skin in 24 h were greatest for IPA, followed by EtOH and IPM, respectively. The vehicle effect was consistent between intact SC absorption and total chemical skin absorption and penetration, as well as SC lipid absorption and chemical penetration through skin, suggesting intercellular transport as a main pathway of skin penetration for model chemicals. These results suggest the potential to predict vehicle effects on skin permeability with simple SC absorption assays. As decontamination was applied 30 min after chemical exposure, significant vehicle effects on chemical SC partitioning and percutaneous penetration also suggest that skin decontamination efficiency is vehicle dependent, and an effective decontamination method should act on chemical solutes in the lipid domain.
authors.affiliation: 1 Department of Chemical and Physical Biology, Harvard University, Cambridge, MA, USA.
authors.forename: Alissa
authors.initials: A
authors.lastname: Zhang
authors.affiliation: 2 Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Eui-Chang
authors.initials: EC
authors.lastname: Jung
authors.affiliation: 2 Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Hanjiang
authors.initials: H
authors.lastname: Zhu
authors.affiliation: 3 Skin & Cosmetic Research Department, Shanghai Skin Disease Hospital, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zou
authors.affiliation: 2 Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Hui
authors.affiliation: 2 Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Maibach
mesh_terms: D019840:2-Propanol / Q000494:pharmacology; D000328:Adult; D019817:Benzoic Acid / Q000032:analysis / Q000493:pharmacokinetics; D001596:Benzylamines / Q000032:analysis / Q000493:pharmacokinetics; D004817:Epidermis / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D009226:Myristates / Q000494:pharmacology; D009281:Naphthalenes / Q000032:analysis / Q000493:pharmacokinetics; D014677:Pharmaceutical Vehicles / Q000494:pharmacology*; D012869:Skin Absorption / Q000187:drug effects*
chemical_list: D001596:Benzylamines; D009226:Myristates; D009281:Naphthalenes; D014677:Pharmaceutical Vehicles; C008205:isopropyl myristate; D000431:Ethanol; D019817:Benzoic Acid; C067594:butenafine; D019840:2-Propanol
keywords: Vehicle effect; percutaneous absorption; skin barrier; skin reservoir; stratum corneum