Construction Of Intestinal-liver-breast Cancer Biomimetic Chip And Its Applications

Pharmacokinetics-Pharmacodynamics(PK-PD)is an important part of preclinical studies of drugs.It can clarify the absorption,distribution,metabolism and excretion of drugs after entering the human body and their effects on drugs through the process of time.It also can reveal the kinetics of drug effects over time and concentration.PK-PD is a process that involves multi-organ and multi-functional,so the research vectors are mainly whole animals such as rats,mice,rabbits and the like.The use of whole animals,on the one hand,increased the use of drugs,hindering more candidate compounds to carry out PK-PD studies.On the other hand,the species difference between animals and humans may lead to a large deviation between pre-clinical metabolic/pharmacodynamic parameters and clinical data.The microfluidic chip can precisely control the fluid at the micro scale and form a network through the microchannel,which is highly integrated,small in volume and high in flux.Based on the microfluidic technique,the microfluidic organ chip can be constructed,and a plurality of organ-related cells are seeded on the chip according to the corresponding in vivo structure.Crosstalk connections between cells or tissues can be connected through microchannels and pump valves,thereby simulating physiological characteristics or functions in vivo.In this paper,based on microfluidic technology,a multi-organ chip containing intestinal,liver,breast cancer and elimination functions was constructed.In this chip,human colon cancer cell line Caco-2 cells and human umbilical vein endothelial cell line HUVEC cells constituted the intestinal module,human hepatoma cell line HepG2 cells and HUVEC cells constituted the liver module,human breast cancer cell line MCF-7 cells and HUVEC cells constituted the breast cancer module,and the dialysis membrane of the dialysis membrane simulated the kidney elimination function.It also contained intestinal circulation channels,main circulation channels and elimination channels to provide nutrients for different modules.The pharmacokinetics(PK)of the chip was then investigated by the propranolol concentration in the main circulating culture medium over time.The pharmacodynamics(PD)of the chip was studied by using the antitumor drugs cyclophosphamide,paclitaxel and capecitabine to inhibit MCF-7 cells in the chip.The results obtained were similar to those reported in the literature,indicating that the multi-organ chip could achieve drug PK-PD evaluation.It was more advantageous than the traditional drug screening platform in vitro evaluation,and could be used for screening preclinical drug research,and provided a new in vitro screening method for preclinical PK-PD studies.