Skin-on-a-Chip Device for Ex Vivo Monitoring of Transdermal Delivery of Drugs—Design, Fabrication, and Testing

Abstract

To develop proper drug formulations and to optimize the delivery of their active ingredients through the dermal barrier, the Franz diffusion cell system is the most widely used in vitro/ex vivo technique. However, different providers and manufacturers make various types of this equipment (horizontal, vertical, static, flow-through, smaller and larger chambers, etc.) with high variability and not fully comparable and consistent data. Furthermore, a high amount of test drug formulations and large size of diffusion skin surface and membranes are important requirements for the application of these methods. The aim of our study was to develop a novel Microfluidic Diffusion Chamber device and compare it with the traditional techniques. Here the design, fabrication, and a pilot testing of a microfluidic skin-on-a chip device are described. Based on this chip, further developments can also be implemented for industrial purposes to assist the characterization and optimization of drug formulations, dermal pharmacokinetics, and pharmacodynamic studies. The advantages of our device, beside the low costs, are the small drug and skin consumption, low sample volumes, dynamic arrangement with continuous flow mimicking the dermal circulation, as well as rapid and reproducible results.

Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic “Skin-On-A-Chip” Microfluidic Device

“…Similar to Franz-diffusion cell system, the polydimethylsiloxane-based microfluidic chip is composed of three functional elements: on top there is a donor compartment where the examined formulation was placed, on the bottom there is a receptor compartment, and an integrated skin sample was placed in the middle ( Figure 2 ), as described in detail in our previous paper [ 11 ].…”

“…The major drawbacks of in vitro skin absorption studies performed using the gold standard, i.e., static Franz diffusion cells, is the absence of capillary blood flow and the large tissue and formulation requirements. In our newly developed skin-on-a chip microfluidic device, microcirculation is mimicked by a dynamic flow-through system [ 11 ]. Furthermore, less tissue, drug and additives are needed.…”

Development of Skin-On-A-Chip Platforms for Different Utilizations: Factors to Be Considered

“…The excellent availability is also an essential point of the use of excised porcine skins. Rat skin is also widely used for dermal penetration studies [ 24 , 25 , 26 ]. Rat skin is employed in the plant protection field for toxicology studies and in-vivo skin absorption studies (transdermal microdialysis).…”

Microfluidic Skin‐on‐a‐Chip Models: Toward Biomimetic Artificial Skin

“…Lukács et al developed an SoC for in vitro / ex vivo monitoring of particle penetration through the skin barrier. [ 117 ] The platform comprises three functional cells: i) drug delivery compartment, ii) skin sample, and iii) receptor compartment. The drug to be examined is contained in the drug delivery compartment, which is located above the skin equivalent.…”