Intestine-kidney system for simulating drug absorption process in vivo based on microfluidic chip
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A microfluidic chip and systemic absorption technology, applied in the field of intestinal-kidney system, can solve problems such as unconsidered drug process, and achieve the effect of reducing the failure rate
Active Publication Date: 2021-10-15
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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Problems solved by technology
Most of the existing work focuses on the evaluation of the toxicity of drugs directly to the kidney, without considering the actual process of the drug in vivo. It is of great significance to build an intestinal-kidney model to simulate the absorption process of drugs in vivo to evaluate renal toxicity.
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Embodiment 1
[0040] Design and fabricate microfluidic chips, with structures such as figure 1 shown. The microfluidic chip is mainly composed of a top chip, a porous filter membrane, and a bottom chip. sealing;
[0041] The top chip is formed by connecting the U-shaped top chip main channel 1 and the top chip main channel entrance 11;
[0042] The bottom chip consists of left main channel 3, right main channel 6, collagen channel 7, collagen channel entrance 8, bottom chip left main channel entrance 9, and bottom chip right main channel entrance 10. Collagen channel 7 is connected to the left Main channel 3, right connected to right main channel 6;
[0043] The main channel 1 of the top chip is connected to the main channel 3 on the left side of the bottom chip through the porous filter membrane 5;
[0044] The main channel 3 on the left side of the bottom chip is I-shaped, the main channel 6 on the right side of the bottom chip is U-shaped, and the collagen channel 7 of the bottom chi...
Embodiment 2
[0050] Evaluation and application of drug nephrotoxicity
[0051] Digoxin has nephrotoxicity, cholestyramine can reduce the intestinal absorption of digoxin, and verapamil can increase the intestinal absorption of digoxin, and the nephrotoxicity changes accordingly.
[0052] Construction of the gut-kidney chip. The upper layer of the chip channel was added with digoxin (Dig) 80 μM, digoxin (Dig) 80 μM combined with cholestyramine (Col) 200 μg / mL, digoxin (Dig) 80 μM combined with verapamil (Ver) 20 μM The cells were cultured in culture medium, and after 48 hours of treatment, the culture medium in the main channel of the lower chip was collected for LDH leakage detection, and the results were as follows figure 2 as shown in c. It can be seen that the LDH leakage of digoxin combined with cholestyramine is lower than that of digoxin alone; the LDH leakage of digoxin combined with verapamil is higher than that of digoxin alone. Affected digoxin nephrotoxicity. Quantitative t...
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Abstract
The invention provides an intestinal-kidney system based on a microfluidic chip for simulating the absorption process of drugs in vivo. The microfluidic chip is mainly composed of a top chip, a porous filter membrane and a bottom chip. The top chip is seeded with intestinal cells, which can simulate the absorption process of drugs in the body; the bottom chip is mainly connected by the left main channel and the right main channel through collagen channels. Inoculate glomerular microtissues in the left main channel, grow glomerular microtissues at the hemispherical interface between the left main channel and the collagen channel by side culture, and form a cell barrier. The right main channel is used as a collection area, which can be observed The glomerular filtration function, and the nephrotoxicity caused by the chemical composition of the drug after intestinal absorption affect the glomerular filtration function. Toxic effects due to the effect of different drug combinations on absorption can be observed. The construction of a drug toxicity evaluation system that simulates the absorption process in vivo, and its application in the evaluation of nephrotoxicity after drug absorption.
Description
technical field [0001] The invention relates to the technical field of applying microfluidic chip technology to the construction of a toxicity evaluation system, in particular to an intestinal-kidney system based on a microfluidic chip to simulate the absorption process of drugs in vivo. Background technique [0002] Animal experiments occupy an extremely important position in modern medicine and biology, but funding and animal ethics have also become unavoidable issues. Combining microfluidic technology and bioscience technology, an "organ chip" has been created, which can replicate the functions of human organs with microchips, making medical experiments easier. [0003] Oral administration, as a traditional way of administration, is widely accepted by people because of its relative convenience and safety. The absorption process is one of the key factors determining the bioavailability of orally administered drugs. The small intestine is the main site of oral drug absorp...
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