Dissolution Behavior and Biodurability of Ingested Engineered Nanomaterials in the Gastrointestinal Environment

Engineered nanomaterials (ENM) are extensively used as food additives in numerous food products, and at present, little is known about the fate of ingested ENM (iENM) in the gastrointestinal (GI) environment. Here, we investigated the dissolution behavior, biodurability, and persistence of four major iENM (TiO₂, SiO₂, ZnO, and two Fe₂O₃) in individual simulated GI fluids (saliva, gastric, and intestinal) and a physiologically relevant digestion cascade (saliva → gastric → intestinal) in the fasted state over physiologically relevant time frames. TiO₂ was found to be the most biodurable and persistent iENM in simulated GI fluids with a maximum of only 0.42% (4 μM Ti⁴⁺ ion release) dissolution in cascade digestion, followed by iron oxides, of which the rod-like morphology was more biodurable and persistent (0.7% maximum dissolution, 8.7 μM Fe³⁺) than the acicular one (2.27% maximum dissolution, 16.7 μM Fe³⁺) in the cascade digestion, respectively. SiO₂ and ZnO were less biodurable than Fe₂O₃, with 65.5% (416 μM Si⁴⁺) and 100% (1718.1 μM Zn²⁺) dissolution in the gastric phase, respectively. In the intestinal phase, however, Si⁴⁺ ions reprecipitated, possibly due to sudden pH changes, while ZnO remained completely dissolved. These observations were also confirmed using high-resolution particle size and concentration, and electron microscopy, time-dependent analysis. In terms of decreasing biodurability and persistence in the simulated GI environment, the tested nanomaterials can be ranked as follows: TiO₂ ≫ rod-like Fe₂O₃ > acicular Fe₂O₃ ≫ SiO₂ > ZnO, which is in agreement with limited animal biokinetics data. Chronic uptake of these iENM as particles or ions by the GI tract, especially in the presence of a food matrix and authentic digestive media, and associated implications for human health warrants further investigation.