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.

Fig. 1

A Schematic illustration of the skin and main penetration routes, insert showing the lipid bilayers between corneocytes. Route A: across the lipid bilayers (intercellular route); Route B: across the corneocytes and lipid bilayers (intracellular route); Route C: along hair follicles and sweat glands

Fig. 2

Schematic illustration of the placental barrier as a cross section of a human placental villus. The placental barrier consists of two layers: the syncytiotrophoblast and cytotrophoblast, the latter forming a discontinuous layer. The basal plasma membrane (BM) of the syncytiotrophoblast is oriented towards the foetal circulation, while the maternal-facing microvillous plasma membrane (MVM) faces the maternal blood compartment

Fig. 3

Two-compartment cell culture system contains a permeable cell culture insert, separating two compartments in a Transwell. Cells are seeded and cultured on the inserts to form a barrier between the two compartments

Fig. 4

In vitro diffusion chamber to test bioavailability of nanoparticles across the skin barrier