Development of a standardized food model for studying the impact of food matrix effects on the gastrointestinal fate and toxicity of ingested nanomaterials

Abstract

Food matrix effects impact the bioavailability and toxicity of pharmaceuticals, nutraceuticals, pesticides, and engineered nanomaterials (ENMs). However, there are currently no standardized food models to test the impact of food matrix effects using in vitro gastrointestinal models. The purpose of this study was to establish a standardized food model (SFM) for evaluating the toxicity and fate of ingested ENMs and then to assess its efficacy by examining the impact of food matrix effects on the toxicity of TiO2 nanoparticles. The formulation of the SFM was based on the average composition of the US diet: 3.4% protein (sodium caseinate); 4.6% sugar (sucrose); 5.2% digestible carbohydrates (modified corn starch); 0.7% dietary fiber (pectin); 3.4% fat (corn oil); and, 0.5% minerals (sodium chloride). The SFM consisted of an oil-in-water emulsion suitable for use in both wet and dried forms. The dried form was produced by spray drying the emulsion to improve its handling and extend its shelf-life. The particle size (D32 = 135 nm), surface charge (−37.8 mV), viscosity, color (L*, a,* b* = 82.1, −2.5, 1.3), and microstructure of the wet SFM were characterized. The hydration properties, flowability (repose angle ≈ 27.9°; slide angle ≈ 28.2°), and moisture sorption isotherms of the dry SFM were comparable to commercial food powders. The potential gastrointestinal fate of the SFM was determined using a simulated gastrointestinal tract, including mouth, stomach, and small intestine steps. Conversion of the SFM into a powdered form did not impact its gastrointestinal fate. A nanotoxicology case study with TiO2 nanoparticles exposed to a tri-culture epithelial cell model showed that food matrix effects reduced ENM cytotoxicity more than 5-fold. The SFM developed in the current study could facilitate studies of the impact of food matrix effects on the gastrointestinal fate and toxicity of various types of food NPs.

Synthesis and Physicochemical Transformations of Size‐Sorted Graphene Oxide during Simulated Digestion and Its Toxicological Assessment against an In Vitro Model of the Human Intestinal Epithelium

“…It has already been shown that certain ENMs have the capacity to alter the bioavailability of nutrients [59] while others may increase the bioavailability of noxious agents, like pesticides. [57] In addition, food matrix effects have been shown to modulate the bioactivity of ENMs, [32,35] and the gut microbiome and proteome of animals is known to be sensitive to the presence of chemically active particulates. [28,29,60] Therefore, we plan to apply the methods developed here to interrogate the physicochemical transformations, toxicological assessment, and effect on gut microbiome and proteome of GO in the presence of more complex food models.…”

“…[30] Still, there are knowledge gaps regarding the toxicokinetics of ingested ENMs following absorption from the GIT, their acute and chronic effects on the gastrointestinal barrier, and their toxicodynamics, including biotransformations as they undergo digestion. Food matrix may further modulate the response of biological systems to ingested ENMs [31,32] and complicate the identification of physical and chemical alterations which might govern their toxicological impact. These alterations include biodissolution, [33] biomolecular corona formation, [34] and morphological changes, like agglomeration.…”

The Food Matrix and the Gastrointestinal Fluids Alter the Features of Silver Nanoparticles

“…[38] Due to their high reactivity, NMs might interact with food components, such as carbohydrates, lipids, proteins, and minerals, which may influence their size, charge, agglomeration state, and surface composition. [35,37,39,40] Besides, once ingested, AgNPs pass through the GIT in which physiological parameters (e.g., pH, ionic strength, protein composition) are constantly evolving and thus influencing the features of AgNPs throughout the digestion process. [38,41,42] As toxic effects of NMs are related to their physicochemical properties, [21,43] all the alterations that could take place before AgNPs attain the intestinal cells might affect their potential toxicity [35,39] and must therefore be included in cytotoxicity investigations to realize an accurate risk assessment.…”

“…[35,37,39,40] Besides, once ingested, AgNPs pass through the GIT in which physiological parameters (e.g., pH, ionic strength, protein composition) are constantly evolving and thus influencing the features of AgNPs throughout the digestion process. [38,41,42] As toxic effects of NMs are related to their physicochemical properties, [21,43] all the alterations that could take place before AgNPs attain the intestinal cells might affect their potential toxicity [35,39] and must therefore be included in cytotoxicity investigations to realize an accurate risk assessment. [37] The European Food Safety Authority (EFSA) has published a guidance in which recommendations were given for risk assessment of nanomaterials used in the food chain.…”

Transformation of Nanomaterials and Its Implications in Gut Nanotoxicology

“…Marked reduction in toxicity was observed in tri‐culture epithelial cell models following exposure to E171 TiO 2 transformed through their interaction with a standard food model. [ 129 ] ENM speciation change was also noted to affect ENM induced toxicity, demonstrated by a reduction in observed ecotoxicity caused by the transformation of Ag ENMs to Ag 2 S. [ 6b,130 ] Therefore, Ag ENMs transformation to Ag 2 S and AgCl species occurring due to their gastric dissolution and interaction with macromolecules along the GIT could reduce intestinal toxicity. Notably, transformation of E171 TiO 2 have been noted to increase the bioavailability and, hence, toxicity of the pesticide, boscalid, in a small intestine tri‐culture model.…”