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 ≈ 28.2o), 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 >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.