Development of an integrated in vitro model for the prediction of oral bioavailability of nanoparticles

Title of the PhD thesis: Development of an integrated in vitro model for the prediction of oral bioavailability of nanoparticles The number of food-related products containing nanoparticles (NPs) increases. To understand the safety of such products, the potential uptake of these NPs following consumption needs to be assessed. In normal safety assessment studies this is investigated using animal models. For scientific, ethical and economical reasons, there is a demand to refine, reduce and replace animal testing by developing in vitro alternatives for hazard characterization. In this thesis an in vitro model for the prediction of the uptake of NPs in the human body after consumption was developed. The model consists of two parts. The first part is a laboratory incubation model mimicking human digestion in mouth, stomach and intestine. For the second part, human intestinal wall cells are used to assess the uptake of nanoparticles. The two models were combined into the integrated in vitro model to take into consideration the potential effect of digestion on nanoparticle uptake in the gut. The main outcome of the work is that the cell-based integrated in vitro model can be used to evaluate which NPs are likely taken up by the body at the highest rate. The size of NPs and the type of chemical groups on their surface greatly influenced the uptake of NPs. The developed model can be used to prioritize the NPs for additional investigations. Using this model in the safety assessment of NPs would reduce the number of animals used in safety assessment.