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Generation of Heterogeneous Drug Gradients Across Cancer Populations on a Microfluidic Evolution Accelerator for Real-Time Observation
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Multiorgan-on-a-chip for cancer drug pharmacokinetics-pharmacodynamics (PK-PD) modeling and simulations

Abdurehman Eshete Mohammed1,2, Filiz Kurucaovalı3, Devrim Pesen Okvur4

  • 1Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey. abdurehman.eshete@wu.edu.et.

Journal of Pharmacokinetics and Pharmacodynamics
|December 4, 2024
PubMed

Insights

A novel multiorgan-on-a-chip (MOC) device with integrated liver and breast compartments was developed. This MOC aids in evaluating cancer drug efficacy and safety through pharmacokinetic-pharmacodynamic (PK-PD) modeling for improved preclinical trials.

Area of Science:

  • Biomedical Engineering
  • Drug Development
  • Cancer Research

Background:

  • Cancer poses a significant global health challenge due to drug resistance, limited efficacy, and safety concerns.
  • Developing effective and safe cancer therapeutics requires robust preclinical evaluation methods.

Purpose of the Study:

  • To design and fabricate a novel multiorgan-on-a-chip (MOC) device integrating breast and liver compartments.
  • To utilize the MOC for pharmacokinetic-pharmacodynamic (PK-PD) modeling and simulation of cancer drugs.
  • To assess the safety and efficacy of drug dosing regimens in a preclinical setting.

Main Methods:

  • A multiorgan-on-a-chip (MOC) device with breast and liver compartments was designed using AutoCAD and 3D printed.
  • Cell viability was assessed using Alamar blue dye to generate pharmacodynamics (PD) data.
  • Drug concentrations were analyzed using HPLC to generate pharmacokinetics (PK) data, followed by PK-PD modeling and simulation.

Main Results:

  • A unique MOC device was successfully fabricated without the need for sealing or assembly.
  • The MOC device demonstrated functionality in generating PK and PD data for drug evaluation.
  • PK-PD modeling and simulation identified optimal drug dosing regimens for safety and efficacy.

Conclusions:

  • The developed MOC provides a functional platform for integrated PK-PD analysis.
  • This novel MOC facilitates the evaluation of cancer drug efficacy and safety in preclinical trials.
  • The MOC technology has the potential to enhance the drug development process for cancer therapeutics.
Keywords:
Breast cancerEfficacyMultiorgan-on-a-chipPharmacodynamicsPharmacokineticsPharmacometricsSafety

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