Prediction of Oral Absorption of Nanoparticles from Biorelevant Matrices Using a Combination of Physiologically Relevant In Vitro and Ex Vivo Models

The application of nanoparticles (NPs) in food products is ever increasing. For consumer safety it is essential to know the human oral bioavailability of these NPs. In the present study, a combination of physiologically relevant in vitro and ex vivo models are presented, which combined are considered to predict human intestinal digestion and absorption of NPs more accurately than commonly applied animal or cellular studies. First, a computer controlled dynamic in vitro gastrointestinal model (tiny- TIM) is used for simulation of the digestive processes upon gastro-intestinal passage of non-biodegradable aminated, carboxylated, or unmodified fluorescent polystyrene NPs (PS-NPs). Then, the pretreated (digested) PS-NPs were consequently evaluated for absorption using ex vivo porcine intestinal tissue. In this study, we found that the digestion of non-biodegradable aminated, carboxylated, or unmodified fluorescent polystyrene NPs (PS-NPs) leads to different bioaccessible concentrations, with unmodified PS-NP concentrations being 3.5 – and 4.5-fold lower than the aminated and carboxylated PS-NPs, respectively. In addition, we observed a reduced absorption of PS-NPs by ex vivo porcine intestinal tissue from the digestive matrix when compared to the absorption of their undigested counterparts in Krebs-Ringer Bicarbonate (KRB) buffer. The current results prove that oral absorption of PS-NPs in humans is to be expected in vivo. In the risk assessment of potential oral exposure to NPs in food products it is therefore key that the exposure and hazard assessment are performed with the NPs in physiologically relevant conditions, since this may influence the absorption and hazard properties of the NPs.