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 is to demonstrate the successful delivery of active ingredients, to predict the risks related to the exposure to potentially toxic molecules or to prove 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 while increasing reproducibility, through a 3R (reduce replace, refine) approach.
Interestingly, the Franz Diffusion Cell (FDC) (Franz, 1975), which is the most common used Diffusion Cell for dermal absorption assays, highlighted some limitations and issues, like the non-homogeneous fluid flow in the receiving chamber, the static environment in the donor chamber, air bubble formations, poor high throughput of the assay. 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 and surrogates. MIVO®, which 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 properly customized with respect to standard methods and OECD guidelines, in terms of skin fixation, physiological controlled flows under the skin barrier mimicking the physiological capillary circulation, de-bubbling and high throughput sampling.
This study highlighted in MIVO® reliable and comparable penetration kinetics, compared with FDC, both using the artificial Strat-M® membrane and pig ear skin. Surprisingly, the testing automatization and reproducibility of results were much improved when MIVO® was adopted as diffusive chamber (standard deviations lower than 2%), opening new perspectives for dermal absorption and the related guidelines.

Compliant with OECD428 guidelines

• Fresh or non-viable skin, skin surrogates
• Donor and receiver compartments physically separated
• Receptor fluid easily sampled at different time-points Controlled temperature
• Controlled fluid flow of the receptor fluid

Advantages

• More reproducible pumping driven fluid flow
• More reliable flow mimicking in vivo blood flow
• Higher scalability: multiple MIVO^® chambers connected in parallel
• Easy sampling compliant with multichannel pipettes
• Miniaturization of the donor/receptor volume for higher sensitivity of the chemical measurements
• Efficient debubbling system increasing reproducibility