title: Progress and future of in vitro models to study translocation of nanoparticles.
abstract: The increasing use of nanoparticles in products likely results in increased exposure of both workers and consumers. Because of their small size, there are concerns that nanoparticles unintentionally cross the barriers of the human body. Several in vivo rodent studies show that, dependent on the exposure route, time, and concentration, and their characteristics, nanoparticles can cross the lung, gut, skin, and placental barrier. This review aims to evaluate the performance of in vitro models that mimic the barriers of the human body, with a focus on the lung, gut, skin, and placental barrier. For these barriers, in vitro models of varying complexity are available, ranging from single-cell-type monolayer to multi-cell (3D) models. Only a few studies are available that allow comparison of the in vitro translocation to in vivo data. This situation could change since the availability of analytical detection techniques is no longer a limiting factor for this comparison. We conclude that to further develop in vitro models to be used in risk assessment, the current strategy to improve the models to more closely mimic the human situation by using co-cultures of different cell types and microfluidic approaches to better control the tissue microenvironments are essential. At the current state of the art, the in vitro models do not yet allow prediction of absolute transfer rates but they do support the definition of relative transfer rates and can thus help to reduce animal testing by setting priorities for subsequent in vivo testing.
authors.affiliation: Department of Toxicogenomics, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands.
authors.forename: Hedwig M
authors.initials: HM
authors.lastname: Braakhuis
authors.forename: Samantha K
authors.initials: SK
authors.lastname: Kloet
authors.forename: Sanja
authors.initials: S
authors.lastname: Kezic
authors.forename: Frieke
authors.initials: F
authors.lastname: Kuper
authors.forename: Margriet V D Z
authors.initials: MV
authors.lastname: Park
authors.forename: Susann
authors.initials: S
authors.lastname: Bellmann
authors.forename: Meike
authors.initials: M
authors.lastname: van der Zande
authors.forename: Séverine
authors.initials: S
authors.lastname: Le Gac
authors.forename: Petra
authors.initials: P
authors.lastname: Krystek
authors.forename: Ruud J B
authors.initials: RJ
authors.lastname: Peters
authors.forename: Ivonne M C M
authors.initials: IM
authors.lastname: Rietjens
authors.forename: Hans
authors.initials: H
authors.lastname: Bouwmeester
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D018920:Coculture Techniques; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000379:methods; D008954:Models, Biological; D053758:Nanoparticles / Q000378:metabolism*; D012377:Rodentia; D014018:Tissue Distribution