Size and surface modification of amorphous silica particles determine their effects on the activity of human CYP3A4 in vitroReport as inadecuate




Size and surface modification of amorphous silica particles determine their effects on the activity of human CYP3A4 in vitro - Download this document for free, or read online. Document in PDF available to download.

Nanoscale Research Letters

, 9:651

First Online: 02 December 2014Received: 21 October 2014Accepted: 26 November 2014

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.

KeywordsNanomaterials Silica nanoparticles Size Surface modification CYP3A4 Human liver microsomes AbbreviationsCYP3A4cytochrome P450 3A4

HLMshuman liver microsomes

LDHlactate dehydrogenase

LIPAluciferin-isopropyl acetal.

Electronic supplementary materialThe online version of this article doi:10.1186-1556-276X-9-651 contains supplementary material, which is available to authorized users.

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Author: Shunji Imai - Yasuo Yoshioka - Yuki Morishita - Tokuyuki Yoshida - Miyuki Uji - Kazuya Nagano - Yohei Mukai - Haruhiko Kam

Source: https://link.springer.com/







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