A new fluidic microphysiological system for improving the reproducibility of skin absorption assay

Dermal absorption assays are employed to assess the absorption kinetics of different molecules. Depending on the application field (pharmaceutics, cosmetics, toxicology), the aim of dermal absorption assays isto demonstrate the successful delivery of active ingredients, to predict the risks related to the exposure topotentially toxic molecules or to proof the absence of absorption of specific substances classes. To align the inter-laboratory data, OECD TG 428 guideline defines a methodologies standardization, for reducing variability whileincreasing reproducibility, through a 3R (reduce replace, refine) approach.

Interestingly, the Franz Diffusion Cell (FDC) (Franz, 1975), which is the most common used Diffusion Cell fordermal absorption assays, highlighted some limitations and issues, like the non-homogeneous fluid flow in thereceiving chamber, the static environment in the donor chamber, air bubble formations, poor high throughput of theassay. We then perform a comparative study between Franz Diffusion Cell and MIVO®, a novel patented micro-physiological system (MPS), evaluating the diffusion of the reference compound, using both excised skins andsurrogates. MIVO®, that has been already successfully validated for gut absorption assays (Marrella et al., 2020a),tumour cells intravasation (Cavo et al., 2018) and cancer drug testing (Marrella et al., 2020b), has been properlycustomized with respect of standard methods and OECD guidelines, in terms of skin fixation, physiologicalcontrolled flows under the skin barrier mimicking the physiological capillary circulation, de-bubbling and highthroughput sampling.

This study highlighted in MIVO® reliable and comparable penetration kinetics, compared with FDC, both using theartificial Strat-M® membrane and pig ear skin. Surprisingly, the testing automatization and reproducibility of resultswere much improved when MIVO® was adopted as diffusive chamber (standard deviations lower than 2%), opening new perspectives for dermal absorption and the related guidelines.

• Conference: MPS World Summit 2021, Virtual Event
• Authors: Marzagalli M. – Pulsoni I. – Aiello M. – Scaglione S.