title: Microreactor microfluidic systems with human microsomes and hepatocytes for use in metabolite studies.
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.
authors.affiliation: Department of Chemical Engineering, The Pennsylvania State University, University Park, PA 16802-4420, USA.
authors.forename: Jeanna C
authors.initials: JC
authors.lastname: Zguris
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Itle
authors.forename: Daniel
authors.initials: D
authors.lastname: Hayes
authors.forename: Michael V
authors.initials: MV
authors.lastname: Pishko
mesh_terms: D001681:Biological Assay / Q000295:instrumentation* / Q000379:methods; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002478:Cells, Cultured; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005434:Flow Cytometry / Q000295:instrumentation* / Q000379:methods; D017022:Flow Injection Analysis / Q000295:instrumentation* / Q000379:methods; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D008904:Miniaturization; D004364:Pharmaceutical Preparations / Q000008:administration & dosage
chemical_list: D004364:Pharmaceutical Preparations