In recent years, microphysiological devices have gained interest for faithfully replicating in vivo microenvironments and interactions between tissues. However, these systems are still scarce in cosmetics testing. Here, HepaRG-stellate spheroids and reconstructed human epidermis models were used in a multi-organ chip to model skin tissue and test pharmacokinetics/dynamics and toxicology of hyperforin and permethrin. The results showed that exposure to these compounds did not alter the normal metabolic capacities of the tissues and the dermis remained unaltered. Moreover, chronic application of the compounds was only reflected on higher concentrations of the compounds themselves but not their metabolites, although the expression of certain genes was modulated by route and frequency of compound application. Finally, it was confirmed that the route of application had an influence on the concentration of compounds and their metabolites. These results were highly reproducible and correlated to the in vivo observations. Overall, the researchers provide a multi-tissue microfluidic platform that can be used to evaluate toxicity and metabolization of different topically applied cosmetic ingredients recapitulating biological processes that occur in vivo.
Characterization of application scenario-dependent pharmacokinetics and pharmacodynamic properties of permethrin and hyperforin in a dynamic skin and liver multi-organ-chip model
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