title: Pre-Plated Cell Lines for ADMETox Applications in the Pharmaceutical Industry.
abstract: Membrane transporters significantly modulate membrane permeability of endobiotics and xenobiotics, such as bile acids and drugs, respectively. Various in vitro methods have been established for both ATP-binding cassette (ABC) transporters to examine cellular efflux and uptake, and for solute carriers (SLC) to examine cellular uptake of substrates. Cell-based systems are the models of choice to test drug-transporter interactions as well as drug-drug interactions for research and regulatory purposes, albeit, for low passive permeability substrates of ABC transporters, vesicular uptake assays are also recommended. Commercially available pre-plated cells (e.g., immortalized or transfected) offer a useful alternative to in-house cell culture. Three main methods are known to manufacture pre-plated cultures: regular culture medium with vacuum seal, cryopreserved delivery, and the solid shipping media technology. The regular culture medium and the solid shipping media technologies provide ready-to-use models for end users. Models expressing a broad selection of transporters are available in pre-plated formats for absorption, distribution, metabolism, excretion, and toxicity (ADMETox) studies. Conversely, the application and utility of pre-plated cultures coupled with personal experiences have not been extensively covered in published research papers or reviews, despite availability and significant use of pre-plated products in the pharmaceutical industry. In this overview, we will briefly describe: 1) in vitro tools commonly used for ADMETox testing; 2) methods employed in manufacturing, shipment and preparation of pre-plated cell lines; 3) cell-membrane barrier models currently available in pre-plated format to reproduce passage restriction of physiological barriers to certain compounds; and 4) recommended pre-plated cell lines overexpressing uptake transporters for ADMETox applications.
authors.affiliation: ReadyCell S. L., Barcelona, Spain.|shared first authorship.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Torres
authors.affiliation: Solvo Biotechnology, Budaörs, Hungary.|shared first authorship.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Sáfár
authors.affiliation: Bioinvitro Division, Leitat Technological Center, Terrassa, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Vázquez-Sánchez
authors.affiliation: Solvo Biotechnology, Budaörs, Hungary.
authors.forename: Anita
authors.initials: A
authors.lastname: Kurunczi
authors.affiliation: Solvo Biotechnology, Budaörs, Hungary.
authors.forename: Emese
authors.initials: E
authors.lastname: Kis
authors.affiliation: Solvo Biotechnology, Budaörs, Hungary.
authors.forename: Rémi
authors.initials: R
authors.lastname: Magnan
authors.affiliation: Solvo Biotechnology, Budaörs, Hungary.
authors.forename: Márton
authors.initials: M
authors.lastname: Jani
authors.affiliation: ReadyCell S. L., Barcelona, Spain.|shared senior authorship.
authors.forename: Oriol
authors.initials: O
authors.lastname: Nicolás
authors.affiliation: Solvo Biotechnology, Budaörs, Hungary.|shared senior authorship.
authors.forename: Péter
authors.initials: P
authors.lastname: Krajcsi
mesh_terms: D000818:Animals; D001692:Biological Transport; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002460:Cell Line; D004345:Drug Industry; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D018675:Toxicity Tests
chemical_list: D004364:Pharmaceutical Preparations
keywords: ABC transporters; ADMETox; permeability; pre-plated cell lines; regulatory studies; solute carriers (SLC); transporters