In vitrogastrointestinal digestion increases the translocation of polystyrene nanoparticles in anin vitrointestinal co-culture model

Abstract

The conditions of the gastrointestinal tract may change the physicochemical properties of nanoparticles (NPs) and therewith the bioavailability of orally taken NPs. Therefore, we assessed the impact of in vitro gastrointestinal digestion on the protein corona of polystyrene NPs (PS-NPs) and their subsequent translocation across an in vitro intestinal barrier. A co-culture of intestinal Caco-2 and HT29-MTX cells was exposed to 50 nm PS-NPs of different charges (positive and negative) in two forms: pristine and digested in an in vitro gastrointestinal digestion model. In vitro digestion significantly increased the translocation of all, except the "neutral", PS-NPs. Upon in vitro digestion, translocation was 4-fold higher for positively charged NPs and 80- and 1.7-fold higher for two types of negatively charged NPs. Digestion significantly reduced the amount of protein in the corona of three out of four types of NPs. This reduction of proteins was 4.8-fold for "neutral", 3.5-fold for positively charged and 1.8-fold for one type of negatively charged PS-NPs. In vitro digestion also affected the composition of the protein corona of PS-NPs by decreasing the presence of higher molecular weight proteins and shifting the protein content of the corona to low molecular weight proteins. These findings are the first to report that in vitro gastrointestinal digestion significantly affects the protein corona and significantly increases the in vitro translocation of differently charged PS-NPs. These findings stress the importance of including the in vitro digestion in future in vitro intestinal translocation screening studies for risk assessment of orally taken NPs.

Critical review of the current and future challenges associated with advancedin vitrosystems towards the study of nanoparticle (secondary) genotoxicity

“…Thus, a co-culture of colon epithelial cells (CaCo-2), THP-1 macrophages and MUTZ-3 dendritic cells have been constructed to assess NP toxicity in healthy and diseased conditions (49). Moreover, a model consisting of CaCo-2 cells and another colon epithelial cell line (HT29-MTX) has also been applied to assess the ability of the gut mucosa to change the physico-chemical characteristics of polystyrene NPs (50). …”

Effect of protein corona magnetite nanoparticles derived from bread in vitro digestion on Caco-2 cells morphology and uptake

“…Walczak et al (2015b) investigated polymeric NPs translocation in different in vitro models taking into account the formation of a corona upon exposure to complete cell medium. Afterwards, the same group showed that NPs, if subject of in vitro digestion, express a different corona upon contact with cell culture medium compared to pristine NPs (Walczak et al, 2015a). On the other hand, Lichtenstein et al (2015) studied the impact of food on silver NPs digestion.…”

Non-animal approaches for toxicokinetics in risk evaluations of food chemicals

“…In general, digestion models have been developed to predict i) the release of chemicals from a formulation (dissolution of medicines) (Cascone et al, 2016;Klein, 2010), ii) the release of chemicals from a complex matrix (i.e., bioaccessibility) (Oomen et al, 2003;Versantvoort et al, 2005) or iii) predicting digestion of macronutrients (e.g., Kopf-Bolanz et al, 2012). However, digestion methods are also increasingly used to study the stability of chemicals in the presence of digestive enzymes and the gastro-intestinal pH (e.g., Islam et al, 2014;Peters et al, 2012;Walczak et al, 2015aWalczak et al, , 2012 and in some cases the breakdown by microbiota (Verwei et al, 2016). New types of dynamic models that are gaining increasing attention are microfluidic gut-on-a-chip models, which provide the potential to develop protocols where in vitro cellular models for absorption harbour intestinal microbiota.…”