Microreactor microfluidic systems with human microsomes and hepatocytes for use in metabolite studies

Biomed Microdevices. 2005 Jun;7(2):117-25. doi: 10.1007/s10544-005-1589-9.

Abstract

In the area of drug discovery, high-speed synthesis has increased the number of drug candidates produced. These potential drugs need to be evaluated for their adsorption, distribution, metabolism, elimination, and toxicology (ADMET) properties as early in the drug development stage as possible. Previously, a potential drug's ADMET properties have been found out by using monolayer cell cultures and live animals. These methods can be costly, time-intensive, and impractical for screening the large amount of potential drugs created by combinatorial chemistry. A quick, small, inexpensive, and highly parallel device would be desirable to determine a drug candidate's properties (i.e., metabolism of the drug). Here we fabricate a microfluidic device entrapping human microsomes within poly(ethylene) glycol hydrogels thereby generating an in situ microreactor to assess a drug candidate's metabolic properties that can be coupled to analysis equipment. We show that microsomes can be entrapped without the loss of enzymatic activity during photopolymerization. Additionally, a microreactor utilizing hepatocytes was also created for comparison with the microsome microreactor.

Publication types

  • Evaluation Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biological Assay / instrumentation*
  • Biological Assay / methods
  • Bioreactors*
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods
  • Cells, Cultured
  • Equipment Design
  • Equipment Failure Analysis
  • Flow Cytometry / instrumentation*
  • Flow Cytometry / methods
  • Flow Injection Analysis / instrumentation*
  • Flow Injection Analysis / methods
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Humans
  • Microfluidic Analytical Techniques / instrumentation*
  • Microfluidic Analytical Techniques / methods
  • Microsomes / drug effects
  • Microsomes / metabolism*
  • Miniaturization
  • Pharmaceutical Preparations / administration & dosage

Substances

  • Pharmaceutical Preparations