Skin-on-a-Chip Technology for Testing Transdermal Drug Delivery—Starting Points and Recent Developments

Abstract

During the last decades, several technologies were developed for testing drug delivery through the dermal barrier. Investigation of drug penetration across the skin can be important in topical pharmaceutical formulations and also in cosmeto-science. The state-of- the-art in the field of skin diffusion measurements, different devices, and diffusion platforms used, are summarized in the introductory part of this review. Then the methodologies applied at Pázmány Péter Catholic University are shown in detail. The main testing platforms (Franz diffusion cells, skin-on-a-chip devices) and the major scientific projects (P-glycoprotein interaction in the skin; new skin equivalents for diffusion purposes) are also presented in one section. The main achievements of our research are briefly summarized: (1) new skin-on-a-chip microfluidic devices were validated as tools for drug penetration studies for the skin; (2) P-glycoprotein transport has an absorptive orientation in the skin; (3) skin samples cannot be used for transporter interaction studies after freezing and thawing; (4) penetration of hydrophilic model drugs is lower in aged than in young skin; (5) mechanical sensitization is needed for excised rodent and pig skins for drug absorption measurements. Our validated skin-on-a-chip platform is available for other research groups to use for testing and for utilizing it for different purposes.

Characterization and ex vivo evaluation of excised skin samples as substitutes for human dermal barrier in pharmaceutical and dermatological studies

“…Values showed a decrease with increasing meaurement depth, but remained higher than for the other species. This can be explained by the different structural composition of pig skin (according to the data of the literature the stratum coneum thickness for pig is approximately 12 micron, for mouse 2.9 micron and for rat about 5 micron 29,30 . Also the thickness of the epidermis is different: 52–100 micron for pig, 9.4–13.3 micron for mouse and approximately 21.7 micron for rats 29,30 .…”

Current Advances in Lipid Nanosystems Intended for Topical and Transdermal Drug Delivery Applications

“…Drug diffusion and heat transfer in the dermal layers of the skin can be predicted using mathematical modeling and computational fluid dynamics [ 231 ]. In general, this device consists of three main parts: a set of polymer-based microfluidic channels, a frame that surrounds the microfluidic channel system, and a sample holder that holds and inserts the membrane or skin sample into the membrane chamber [ 232 ]. Additionally, the skin-on-a-chip microfluidic platform enables cost-effective and reliable drug screening as the delivery setup is miniaturised [ 232 ].…”

“…In general, this device consists of three main parts: a set of polymer-based microfluidic channels, a frame that surrounds the microfluidic channel system, and a sample holder that holds and inserts the membrane or skin sample into the membrane chamber [ 232 ]. Additionally, the skin-on-a-chip microfluidic platform enables cost-effective and reliable drug screening as the delivery setup is miniaturised [ 232 ]. Currently, a technology involving the connection of skin-on-a-chip devices to robotic systems for mid-throughput drug screening in the pharmaceutical industry is being validated and optimised [ 231 ].…”

The Synergy between Deep Learning and Organs-on-Chips for High-Throughput Drug Screening: A Review

“…This miniaturized chip based on microfluidics is a platform to mimic the skin and its equivalents in a simple manner. Figure 13 depicts a solution for designing the skin-on-a-chip for testing drug penetration through the skin [ 119 ].…”