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.

Oral uptake of nanoparticles: human relevance and the role of in vitro systems

“…Translocation of TiO 2 NPs in sizes 18, 40-50, 120 and 130 nm were below the detection limit in the majority of the studies (Braakhuis et al 2015). This rate appeared realistic when compared to animal data.…”

How do the physicochemical properties of nanoliposomes affect their interactions with the hCMEC/D3 cellular model of the BBB?

“…In an immortalized mouse cerebral endothelial cell line, the bEnd3 monolayer, it was previously found that the permeability of different solutes (with MW up to 70000) is linearly decreased as solute Stokes radius increases, and that the permeability of quaternary ammonium b-cyclodextrin nanoparticles (QAbCD) with varying zeta potential values, ranging from À11 to +14 is different; the positively charge QAbCD's having higher permeability's (Yuan et al, 2010). In a recent review about in vitro models used to study the translocation of nanoparticles (Braakhuis et al, 2015), particle size is mentioned to affect the translocation of nanoparticles across several cellular models, such as rat alveolar epithelial cell monolayers, as well as cellular models of the placental and intestinal barrier. In fact it is well known that the size and charge of nanoparticles has a profound effect on their (in vivo/ ex-vivo) intestinal transport (Araujo et al, 2014;Jani et al, 1990Jani et al, , 1989.…”

Biomimetics of the pulmonary environment in vitro: A microfluidics perspective

“…While cell cultures grown in petri dishes have been traditionally conducted under immersed conditions, those at an ALI are known to increase monolayer integrity 120,123,126,129 (measured by trans-epithelial electrical resistance, TEER), contribute to well differentiated morphology in primary cells, 130,131 and increase surfactant secretion for AEC II cells 126,129 . Hence, culture methods at an ALI have been increasingly attractive over the past years, 118,132 emphasizing such method as a favourable platform to investigate the epithelial barrier at large 126,129 as well as cytotoxicity in the context of inhaled xenobiotics 132–136 and drug transport 137–139 …”