Assessing orally bioavailable commercial silver nanoparticle product on human cytochrome P450 enzyme activity

Abstract

Nanotechnology produces a wide range of medicinal compounds, including nanoparticulate silver, which are increasingly introduced in various forms for consumer use. As with all medicinal compounds, potential drug interactions are an important consideration for ingested silver nanoparticles. Nanoparticulate silver–drug interactions may be mediated through induced oxidative stress in liver tissue where the majority of systemically bioavailable silver nanoparticles is found. To investigate whether an orally ingested commercially available colloidal silver nanoproduct produces pharmacokinetic interference on select cytochrome P450 enzymes, a prospective, single-blind, controlled in vivo human study using simultaneous administration of standardized probes for P450 enzyme classes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 was conducted. Oral ingestion of a commercial colloidal silver nanoproduct produces detectable silver in human serum after 14 days of dosing. This silver, however, elicits no demonstrable clinically significant changes in metabolic, hematologic, urinary, physical findings or cytochrome P450 enzyme inhibition or induction activity. Given their increasingly broad, diverse human exposures, future characterization of human cytochrome P450 enzyme activity for other systemically bioavailable nanotechnology products are warranted.

• Clinical study
• in vivo
• nanoparticles
• pharmacokinetics
• toxicology

Acknowledgements

The authors acknowledge the nursing support of the University of Utah Center for Clinical and Translational Research towards the conduction of this protocol. Peer-reviewers for this journal are thanked for many high quality and insightful comments that improved this contribution greatly. The authors are grateful for many technical and editorial contributions and suggestions from Dr. D.W. Grainger (University of Utah, USA).

Declaration of interest

The authors disclose no financial, consulting, or personal relationships with other people or organizations that influenced this publication. The manuscript was not under any contractual relationship for review, comment or approval before publication. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number 1ULTR001067. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors declare no conflicts of interests. None of the funding bodies contributed to the study design, data interpretation, or preparation of the manuscript.

This study was presented, in part, at the 2012 Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, Washington, DC (March, 2012).