Abstract
Automated biomimetic systems for the preclinical testing of drugs are of great interest. Here, an in vitro testing platform for in vivo adapted drug absorption studies is presented. It has been designed with a focus on easy handling and the usability of established cell cultivation techniques in standard well plate inserts. The platform consists of a microfluidic device, which accommodates a well plate insert with pre-cultivated cells, and provides a fluid flow with dynamic drug dilution profiles. A low-cost single-board computer with a touchscreen was used as a control unit. This provides a graphical user interface, controls the syringe pump flow rates, and records the transepithelial electrical resistance. It thereby enables automated parallel testing in multiple devices at the same time. To demonstrate functionality, an MDCK cell layer was used as a model for an epithelial barrier for drug permeation testing. This confirms the possibility of performing absorption studies on barrier tissues under conditions close to those in vivo. Therefore, a further reduction in animal experiments can be expected.
Highlights
The development of new drugs is a complex and scientifically demanding task that is time consuming and costly [1,2]
At a dilution profile with 8.3 % min−1 and a total flow rate of 75 μL min−1, the calculated target volumes correspond to the volumes of Pumps 1 and 2 determined experimentally (Figure 6a)
Since the system is flushed with Krebs–Ringer buffer (KRB) buffer before the start of the experiment, the expected concentration becomes effective with a delay
Summary
The development of new drugs is a complex and scientifically demanding task that is time consuming and costly [1,2]. A few of the most promising new drug candidates make it through the clinical test phase successfully and are introduced to the market as approved drugs [3]. To minimize the failure of potential candidates in the most expensive clinical tests, the use of a valid and significant test system in preclinical tests is of particular importance. For testing new drugs in preclinical studies, animal models are traditionally used. Since animal models are expensive, difficult to transfer to humans, and—above all—ethically questionable, they are increasingly being replaced by in vitro cell culture models [4]. Most of the well-established in vitro systems are static and do not have the ability to mimic human in vivo environments, which is detrimental for a reliable prediction of substance behavior in the subsequent clinical studies
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