title: Interactions between nano-TiO2 and the oral cavity: impact of nanomaterial surface hydrophilicity/hydrophobicity.
abstract: Titanium dioxide (TiO2) nanoparticles are available in a variety of oral applications, such as food additives and cosmetic products. Thus, questions about their potential impact on the oro-gastrointestinal route rise. The oral cavity represents the first portal of entry and is known to rapidly interact with nanoparticles. Surface charge and size contribute actively to the particle-cell interactions, but the influence of surface hydrophilicity/hydrophobicity has never been shown before. This study addresses the biological impact of hydrophilic (NM 103, rutile, 20 nm) and hydrophobic (NM 104, rutile, 20 nm) TiO2 particles within the buccal mucosa. Particle characterization was addressed with dynamic light scattering and laser diffraction. Despite a high agglomeration tendency, 10% of the particles/agglomerates were present in the nanosized range and penetrated into the mucosa, independent of the surface properties. However, significant differences were observed in intracellular particle localization. NM 104 particles were found freely distributed in the cytoplasm, whereas their hydrophobic counterparts were engulfed in vesicular structures. Although cell viability/membrane integrity was not affected negatively, screening assays demonstrated that NM 104 particles showed a higher potential to decrease the physiological mitochondrial membrane potential than NM 103, resulting in a pronounced generation of reactive oxygen species.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, 8010, Austria.
authors.forename: Birgit J
authors.initials: BJ
authors.lastname: Teubl
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, 8010, Austria.
authors.forename: Christa
authors.initials: C
authors.lastname: Schimpel
authors.affiliation: Institute of Cell Biology, Histology and Embryology, Research Unit Electron Microscopic Techniques, Medical University of Graz, 8010, Austria; Center for Medical Research, Medical University of Graz, 8010, Austria; BioTechMed, Graz 8010, Austria.
authors.forename: Gerd
authors.initials: G
authors.lastname: Leitinger
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, 8010, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Bauer
authors.affiliation: Center for Medical Research, Medical University of Graz, 8010, Austria; BioTechMed, Graz 8010, Austria.
authors.forename: Eleonore
authors.initials: E
authors.lastname: Fröhlich
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, 8010, Austria; BioTechMed, Graz 8010, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, 8010, Austria; BioTechMed, Graz 8010, Austria. Electronic address: eva.roblegg@uni-graz.at.
authors.forename: Eva
authors.initials: E
authors.lastname: Roblegg
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003412:Cricetulus; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability; D017382:Reactive Oxygen Species / Q000378:metabolism; D013499:Surface Properties; D013552:Swine; D014025:Titanium / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium
keywords: Hydrophilicity/hydrophobicity; Intracellular distribution; Oral cavity; Titanium dioxide nanoparticles; Toxicity