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In Vitro Models of Biological Barriers for Nanomedical Research

Carton, Flavia, Malatesta, Manuela·2022·International Journal of Molecular Sciences
DOI 10.3390/ijms23168910PMC PMC9408841
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Abstract

Nanoconstructs developed for biomedical purposes must overcome diverse biological barriers before reaching the target where playing their therapeutic or diagnostic function. In vivo models are very complex and unsuitable to distinguish the roles plaid by the multiple biological barriers on nanoparticle biodistribution and effect; in addition, they are costly, time-consuming and subject to strict ethical regulation. For these reasons, simplified in vitro models are preferred, at least for the earlier phases of the nanoconstruct development. Many in vitro models have therefore been set up. Each model has its own pros and cons: conventional 2D cell cultures are simple and cost-effective, but the information remains limited to single cells; cell monolayers allow the formation of cell–cell junctions and the assessment of nanoparticle translocation across structured barriers but they lack three-dimensionality; 3D cell culture systems are more appropriate to test in vitro nanoparticle biodistribution but they are static; finally, bioreactors and microfluidic devices can mimicking the physiological flow occurring in vivo thus providing in vitro biological barrier models suitable to reliably assess nanoparticles relocation. In this evolving context, the present review provides an overview of the most representative and performing in vitro models of biological barriers set up for nanomedical research.

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Figure 1 Schematic drawing of an in vitro 2D barrier model made of a culture well with a cell culture insert. Nanoparticles are administered in the medium in the cell insert and monitored for their passage to the lower chamber through the cell monolayer.
Figure 1 Schematic drawing of an in vitro 2D barrier model made of a culture well with a cell culture insert. Nanoparticles are administered in the medium in the cell insert and monitored for their passage to the lower chamber through the cell monolayer.CC BY · PubMed Central
Figure 2 Schematic drawing of an in vitro 3D barrier model. Nanoparticles are administered in the medium and monitored for their penetration into the spheroid.
Figure 2 Schematic drawing of an in vitro 3D barrier model. Nanoparticles are administered in the medium and monitored for their penetration into the spheroid.CC BY · PubMed Central
Figure 3 Schematic drawing of an in vitro barrier model under fluid dynamic conditions. Despite the high heterogeneity of devices described in the literature, the design is in principle the same for bioreactors and microfluidics. Nanoparticles are administered through the inlet chamber, move to the cells in the upper channel due to the flowing medium, and cross the cell monolayer toward the lower channel.
Figure 3 Schematic drawing of an in vitro barrier model under fluid dynamic conditions. Despite the high heterogeneity of devices described in the literature, the design is in principle the same for bioreactors and microfluidics. Nanoparticles are administered through the inlet chamber, move to the cells in the upper channel due to the flowing medium, and cross the cell monolayer toward the lower channel.CC BY · PubMed Central

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Metadata

Authors
Carton, F., & Malatesta, M.
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2022-08-10
Volume
23
Issue
16
Pages
8910
ISSN
1422-0067
DOI
10.3390/ijms23168910
PMC
PMC9408841
Cited by
34
References
8
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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