gut-on-a-chip
The results of RNA-seq have heightened our focus on the potential application of the gut-on-a-chip system in the field of in vitro drug bioavailability evaluation. It is well-established that various orally administered drugs exhibit different levels of absorption across the epithelial barrier in vivo. As a result, an absorption test is essential for each new drug before its clinical application. In this study, we aimed to utilize the gut-on-a-chip system to measure the permeability (Papp) values of seven drugs: Antipyrine, Propranolol hydrochloride, Hydrochlorothiazide, Ranitidine hydrochloride, Atenolol, Sulpiride, and Furosemide. These drugs were selected based on the Biopharmaceutics Classification System Biowaivers Guidance for Industry, and they represent a range of high, medium, and low in vivo permeability with well-documented bioavailability.[31]
After cultivating cells on the chip using the consistent method, we employed high-performance liquid chromatography to measure the drug concentration reaching the bottom channel of the chip following a three-hour drug incubation period (Fig. 5A) . Subsequently, we established a correlation between the drug permeability coefficient and its in-vivo bioavailability. The Papp values were determined using the following formula: Papp = (dQ/dt) / (A ยท c0). In this equation, dQ represents the amount of drug passing through the membrane during the experimental duration, dt denotes the experimental time, A signifies the membrane area, and c0 corresponds to the initial concentration of the drug introduced from the apical side. The experimental results showed a clear positive correlation between the Papp values and bioavailability in both the static and perfused chips (Fig. 5B) . However, the linear fit of the dynamic results was significantly superior, with an R2 value of 0.7085 for the perfused chip and only 0.3081 for the static chip. These findings indicate that the perfused chip holds greater potential as a platform for predicting drug absorption.