title: Size and surface modification of amorphous silica particles determine their effects on the activity of human CYP3A4 in vitro.
abstract: Because of their useful chemical and physical properties, nanomaterials are widely used around the world - for example, as additives in food and medicines - and such uses are expected to become more prevalent in the future. Therefore, collecting information about the effects of nanomaterials on metabolic enzymes is important. Here, we examined the effects of amorphous silica particles with various sizes and surface modifications on cytochrome P450 3A4 (CYP3A4) activity by means of two different in vitro assays. Silica nanoparticles with diameters of 30 and 70 nm (nSP30 and nSP70, respectively) tended to inhibit CYP3A4 activity in human liver microsomes (HLMs), but the inhibitory activity of both types of nanoparticles was decreased by carboxyl modification. In contrast, amine-modified nSP70 activated CYP3A4 activity. In HepG2 cells, nSP30 inhibited CYP3A4 activity more strongly than the larger silica particles did. Taken together, these results suggest that the size and surface characteristics of the silica particles determined their effects on CYP3A4 activity and that it may be possible to develop silica particles that do not have undesirable effects on metabolic enzymes by altering their size and surface characteristics.
authors.affiliation: Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Imai
authors.affiliation: Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshioka
authors.affiliation: Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Morishita
authors.affiliation: Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Tokuyuki
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Uji
authors.affiliation: Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nagano
authors.affiliation: Laboratory of Innovative Antibody Engineering and Design, Center for Drug Innovation and Screening, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mukai
authors.affiliation: Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085, Japan ; The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kamada
authors.affiliation: Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085, Japan ; The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Tsunoda
authors.affiliation: Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Higashisaka
authors.affiliation: Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan ; The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
keywords: CYP3A4; Human liver microsomes; Nanomaterials; Silica nanoparticles; Size; Surface modification