A cell culture system to model pharmacokinetics using adjustable-volume perfused mixing chambers.

Autor: Erickson P; Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08854, USA., Jetley G; Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA., Amin P; Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA., Mejevdiwala A; Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA., Patel A; Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA., Cheng K; Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA., Parekkadan B; Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA; Department of Medicine, Rutgers Biomedical Health Sciences, New Brunswick, NJ 08852, USA. Electronic address: biju.parekkadan@rutgers.edu.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2023 Sep; Vol. 91, pp. 105623. Date of Electronic Publication: 2023 May 24.
DOI: 10.1016/j.tiv.2023.105623
Abstrakt: The pharmacokinetic (PK) profile of a drug is an essential factor in determining its efficacy, yet it is often neglected during in vitro cell culture experiments. Here, we present a system in which standard well plate cultures may be "plugged in" and perfused with PK drug profiles. Timed drug boluses or infusions are passed through a mixing chamber that simulates the PK volume of distribution specific to the desired drug. The user-specified PK drug profile generated by the mixing chamber passes through the incubated well plate culture, exposing cells to in vivo-like PK drug dynamics. The effluent stream from the culture may then optionally be fractionated and collected by a fraction collector. This low-cost system requires no custom parts and perfuses up to six cultures in parallel. This paper demonstrates a range of PK profiles the system can produce using a tracer dye, describes how to find the correct mixing chamber volumes to mimic PK profiles of drugs of interest, and presents a study exploring the effects of differing PK exposure on a model of lymphoma treatment with chemotherapy.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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