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.