A cell culture system to model pharmacokinetics using adjustable-volume perfused mixing chambers.
In vitro model
Lymphoma
Perfusion cell culture
Pharmacokinetics
Residence time distributions
Journal
Toxicology in vitro : an international journal published in association with BIBRA
ISSN: 1879-3177
Titre abrégé: Toxicol In Vitro
Pays: England
ID NLM: 8712158
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
21
12
2022
revised:
03
04
2023
accepted:
19
05
2023
pmc-release:
01
09
2024
medline:
14
7
2023
pubmed:
27
5
2023
entrez:
26
5
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37236431
pii: S0887-2333(23)00072-3
doi: 10.1016/j.tiv.2023.105623
pmc: PMC10526707
mid: NIHMS1906181
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
105623Subventions
Organisme : NIBIB NIH HHS
ID : R01 EB012521
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB028782
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008339
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
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.
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