title: Human skin penetration and local effects of topical nano zinc oxide after occlusion and barrier impairment.
abstract: Public health concerns continue to exist over the safety of zinc oxide nanoparticles that are commonly used in sunscreen formulations. In this work, we assessed the effects of two conditions which may be encountered in everyday sunscreen use, occlusion and a compromised skin barrier, on the penetration and local toxicity of two topically applied zinc oxide nanoparticle products. Caprylic/capric triglyceride (CCT) suspensions of commercially used zinc oxide nanoparticles, either uncoated or with a silane coating, were applied to intact and barrier impaired skin of volunteers, without and with occlusion for a period of six hours. The exposure time was chosen to simulate normal in-use conditions. Multiphoton tomography with fluorescence lifetime imaging was used to noninvasively assess zinc oxide penetration and cellular metabolic changes that could be indicative of toxicity. We found that zinc oxide nanoparticles did not penetrate into the viable epidermis of intact or barrier impaired skin of volunteers, without or with occlusion. We also observed no apparent toxicity in the viable epidermis below the application sites. These findings were validated by ex vivo human skin studies in which zinc penetration was assessed by multiphoton tomography with fluorescence lifetime imaging as well as Zinpyr-1 staining and toxicity was assessed by MTS assays in zinc oxide treated skin cryosections. In conclusion, applications of zinc oxide nanoparticles under occlusive in-use conditions to volunteers are not associated with any measurable zinc oxide penetration into, or local toxicity in the viable epidermis below the application site.
authors.affiliation: Instituto de Ciências Ambientais Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, SP, Brazil; Therapeutics Research Centre, School of Medicine, The University of Queensland, Translational Research Institute, QLD 4102, Australia.
authors.forename: V R
authors.initials: VR
authors.lastname: Leite-Silva
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Translational Research Institute, QLD 4102, Australia.
authors.forename: W Y
authors.initials: WY
authors.lastname: Sanchez
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Studier
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Translational Research Institute, QLD 4102, Australia.
authors.forename: D C
authors.initials: DC
authors.lastname: Liu
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Translational Research Institute, QLD 4102, Australia.
authors.forename: Y H
authors.initials: YH
authors.lastname: Mohammed
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
authors.forename: A M
authors.initials: AM
authors.lastname: Holmes
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Translational Research Institute, QLD 4102, Australia.
authors.forename: E M
authors.initials: EM
authors.lastname: Ryan
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Translational Research Institute, QLD 4102, Australia.
authors.forename: I N
authors.initials: IN
authors.lastname: Haridass
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Translational Research Institute, QLD 4102, Australia.
authors.forename: N C
authors.initials: NC
authors.lastname: Chandrasekaran
authors.affiliation: Becker & Hickl GmbH, Nahmitzer Damm 30, 12277 Berlin, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Becker
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Translational Research Institute, QLD 4102, Australia.
authors.forename: J E
authors.initials: JE
authors.lastname: Grice
authors.affiliation: School of Pharmacy, CHIRI, Curtin University, GPO Box U1987, Perth, WA, Australia. Electronic address: h.benson@curtin.edu.au.
authors.forename: H A E
authors.initials: HA
authors.lastname: Benson
authors.affiliation: Therapeutics Research Centre, School of Medicine, The University of Queensland, Translational Research Institute, QLD 4102, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia. Electronic address: m.roberts@uq.edu.au.
authors.forename: M S
authors.initials: MS
authors.lastname: Roberts
mesh_terms: D000287:Administration, Topical; D005260:Female; D006801:Humans; D053758:Nanoparticles; D012869:Skin Absorption; D015034:Zinc Oxide / Q000008:administration & dosage*
chemical_list: D015034:Zinc Oxide
keywords: Barrier impairment; In-use application; Occlusion; Safety; Skin penetration; Sunscreens; Toxicity; Zinc oxide nanoparticles