title: In vitro gastrointestinal digestion increases the translocation of polystyrene nanoparticles in an in vitro intestinal 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.
authors: a Division of Toxicology , Wageningen University , Wageningen , The Netherlands and.|b RIKILT Wageningen UR , Wageningen , The Netherlands.
authors: Agata P
authors: AP
authors: Walczak
authors: b RIKILT Wageningen UR , Wageningen , The Netherlands.
authors: Evelien
authors: E
authors: Kramer
authors: b RIKILT Wageningen UR , Wageningen , The Netherlands.
authors: Peter J M
authors: PJ
authors: Hendriksen
authors: b RIKILT Wageningen UR , Wageningen , The Netherlands.
authors: Richard
authors: R
authors: Helsdingen
authors: b RIKILT Wageningen UR , Wageningen , The Netherlands.
authors: Meike
authors: M
authors: van der Zande
authors: a Division of Toxicology , Wageningen University , Wageningen , The Netherlands and.
authors: Ivonne M C M
authors: IM
authors: Rietjens
authors: b RIKILT Wageningen UR , Wageningen , The Netherlands.
authors: Hans
authors: H
authors: Bouwmeester
mesh_terms: D001682:Biological Availability; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D004063:Digestion; D004305:Dose-Response Relationship, Drug; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D053758:Nanoparticles / Q000378:metabolism* / Q000633:toxicity; D011137:Polystyrenes / Q000493:pharmacokinetics* / Q000633:toxicity; D000066970:Protein Corona / Q000378:metabolism
chemical_list: D011137:Polystyrenes; D000066970:Protein Corona
keywords: 3Rs principle; ingestion; mucus; protein corona; surface modification