Abstract
The established in vitro tool used for testing the absorption and penetration of chemicals through skin in pharmacology, toxicology and cosmetic science is the static Franz diffusion cell. While widespread, Franz cells are relatively costly, low-throughput and results may suffer from poor reproducibility. Microfluidics has the potential to overcome these drawbacks. In this paper, we present a novel microfluidic skin permeation platform and validate it rigorously against the Franz cell by comparing the transport of 3 model chemicals of varying lipophilicity: caffeine, salicylic acid and testosterone. Permeation experiments through silicone membranes show that the chip yields higher sensitivity in permeant cumulative amounts and comparable or lower coefficients of variation. Using a skin organotypic culture, we show that the chip decreases the effect of unstirred water layers that can occur in static Franz cells. The validation reported herein sets the stage for efficient skin permeation and toxicity screening and further development of microfluidic skin-on-chip devices.
Highlights
Paper toxicology and cosmetic science have a similar need for the development and validation of high-throughput, alternative skin permeation testing methods.The traditional systems for in vitro skin permeation testing are the static Franz and flow-through diffusion cells, in which excised skin or a skin substitute is sandwiched between a donor compartment and a receptor compartment (Fig. 1a)
Using a skin organotypic culture, we show that the chip decreases the effect of unstirred water layers that can occur in static Franz cells
We presented and validated a microfluidic platform for improved, cost-effective in vitro skin permeation testing
Summary
The traditional systems for in vitro skin permeation testing are the static Franz and flow-through diffusion cells, in which excised skin or a skin substitute is sandwiched between a donor compartment and a receptor compartment (Fig. 1a). Sampling of the receptor solution occurs at predetermined times following application of a donor solution. This yields profiles of the concentration or cumulative amount over time of the compound of interest, from which transport parameters can be derived. Franz cells' typical diffusion areas of 1 to 3 cm[2], receptor volumes on the order of a few mL and time-consuming procedures render them relatively costly and low-throughput.[7] In addition, an unstirred water layer (UWL) may form in the static Franz cell when highly permeable membranes and lipophilic chemicals are used. Supplementary experiments and calculation are necessary to assess the effect of the UWL on the chemical's permeability through the membrane.[8,9]
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