Impact of an Artificial Digestion Procedure on Aluminum-Containing Nanomaterials

Abstract

Aluminum has gathered toxicological attention based on relevant human exposure and its suspected hazardous potential. Nanoparticles from food supplements or food contact materials may reach the human gastrointestinal tract. Here, we monitored the physicochemical fate of aluminum-containing nanoparticles and aluminum ions when passaging an in vitro model of the human gastrointestinal tract. Small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), ion beam microscopy (IBM), secondary ion beam mass spectrometry (TOF-SIMS), and inductively coupled plasma mass spectrometry (ICP-MS) in the single-particle mode were employed to characterize two aluminum-containing nanomaterials with different particle core materials (Al, γAlO) and soluble AlCl. Particle size and shape remained unchanged in saliva, whereas strong agglomeration of both aluminum nanoparticle species was observed at low pH in gastric fluid together with an increased ion release. The levels of free aluminum ions decreased in intestinal fluid and the particles deagglomerated, thus liberating primary particles again. Dissolution of nanoparticles was limited and substantial changes of their shape and size were not detected. The amounts of particle-associated phosphorus, chlorine, potassium, and calcium increased in intestinal fluid, as compared to nanoparticles in standard dispersion. Interestingly, nanoparticles were found in the intestinal fluid after addition of ionic aluminum. We provide a comprehensive characterization of the fate of aluminum nanoparticles in simulated gastrointestinal fluids, demonstrating that orally ingested nanoparticles probably reach the intestinal epithelium. The balance between dissolution and de novo complex formation should be considered when evaluating nanotoxicological experiments.

Genotoxicity of Aluminum and Aluminum Oxide Nanomaterials in Rats Following Oral Exposure

“…No correlation between the in vivo genotoxicity of Al NMs and the ionic salt AlCl 3 was observed in our study, and we therefore cannot conclusively determine the potential effect of aluminum ions released from the Al NMs. Although we have previously reported a low solubility of these Al-containing NMs in an in vitro digestion system [25], estimating the solubility of NMs in the intestinal fluid in vivo remains challenging. Therefore, no clear conclusion can be drawn on the role, if any, of metallic ions in the genotoxic effects observed.…”

“…Several parameters of physicochemical characterization in the dispersion stock solution and those provided by the suppliers are summarized in Table 1. A more detailed description of the physicochemical characterization of the two NMs was published previously [25,26].…”

Impact of in vitro digestion on gastrointestinal fate and uptake of silver nanoparticles with different surface modifications

“…These varying conditions can affect the AgNPs physicochemical properties (e.g. agglomeration and dissolution) and accordingly affect their bioavailability and toxicological properties (B€ ohmert et al 2014;Lichtenstein et al 2017;Murdock et al 2008;Sieg et al 2017). Upon reaching the intestine, the biological interactions (e.g.…”

“…AgNPs size and surface chemistry play an important role in their stability, cellular internalization, and transport Mwilu et al 2013). Several in vitro models have been developed to represent the intestinal epithelial barrier (Lefebvre et al 2015) which are exposed to NPs to simulate real-life human exposure conditions to NPs (Nel et al 2006;Sieg et al 2017). Among these model, the co-cultures of monolayers of Caco-2 intestinal cells and HT29-MTX mucus secreting cells are widely used as an in vitro intestinal epithelium model (Bailey, Bryla, and Malick 1996;Georgantzopoulou et al 2015;Lefebvre et al 2015;Stone, Johnston, and Schins 2009).…”

The Vitamin A and D Exposure of Cells Affects the Intracellular Uptake of Aluminum Nanomaterials and Its Agglomeration Behavior: A Chemo-Analytic Investigation

“…The relatively low density of the light metal, its low mass and the complexity of biological matrices complicate the use of widespread analytical techniques like Raman spectroscopy or transmission electron microscopy (TEM). ToF-SIMS analysis [9] has been previously applied for the detection of cerium dioxide particle clusters in rat lung tissue [10] and for the characterization of Al particles in artificial saliva [11]. In this study, we tried to overcome the mentioned analytical limitations by using ToF-SIMS to explore uptake and distribution patterns of Al and Al 2 O 3 NMs in the human keratinocyte cell line HaCaT.…”