4.6 Article

Fabrication and Evaluation of Tubule-on-a-Chip with RPTEC/HUVEC Co-Culture Using Injection-Molded Polycarbonate Chips

Journal

MICROMACHINES
Volume 13, Issue 11, Pages -

Publisher

MDPI
DOI: 10.3390/mi13111932

Keywords

tubule-on-a-chip; metformin; RPTEC; HUVEC; microfluidic chip

Funding

  1. National Research Foundation of Korea (NRF) grant - Korean government (MSIP) [NRF-2020R1A2C2009928]
  2. Technology Innovation Program (or Industrial Strategic Technology Development Program-3D Organ-on-a-Chip-Based new Drug Development Platform Construction Project) - Ministry of Trade, Industry & Energy (MOTIE, Korea) [20008414]

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A microfluidic chip injection molded with polycarbonate was fabricated to simulate the ADME process in the human body after drug administration. The study confirmed higher cell viability with larger pore sizes, better cell culture performance, and enhanced drug secretion.
To simulate the ADME process such as absorption, distribution, metabolism, and excretion in the human body after drug administration and to confirm the applicability of the mass production process, a microfluidic chip injection molded with polycarbonate (injection-molded chip (I-M chip)) was fabricated. Polycarbonate materials were selected to minimize drug absorption. As a first step to evaluate the I-M chip, RPTEC (Human Renal Proximal Tubule Epithelial Cells) and HUVEC (Human Umbilical Vein Endothelial Cells) were co-cultured, and live and dead staining, TEER (trans-epithelial electrical resistance), glucose reabsorption, and permeability were compared using different membrane pore sizes of 0.4 mu m and 3 mu m. Drug excretion was confirmed through a pharmacokinetic test with metformin and cimetidine, and the gene expression of drug transporters was confirmed. As a result, it was confirmed that the cell viability was higher in the 3 mu m pore size than in the 0.4 mu m, the cell culture performed better, and the drug secretion was enhanced when the pore size was large. The injection-molded polycarbonate microfluidic chip is anticipated to be commercially viable for drug screening devices, particularly ADME tests.

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