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

• Published in: Toxicology in vitro Vol. 91; p. 105623
• Main Authors: Erickson, Patrick, Jetley, Gunjan, Amin, Param, Mejevdiwala, Aamena, Patel, Ashna, Cheng, Kelli, Parekkadan, Biju
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2023
• Subjects: Cell Culture Techniques; In vitro model; Lymphoma; Perfusion cell culture; Pharmacokinetics; Residence time distributions; CSTR; Q; Perfusion cell culture; RTD; V; In vitro model; Residence time distributions; PK; Pharmacokinetics; Lymphoma; AUC
• ISSN: 0887-2333; 1879-3177; 1879-3177
• DOI: 10.1016/j.tiv.2023.105623

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. •Pharmacokinetic drug profiles are recapitulated in perfusion cell cultures.•Multiple cultures can be perfused in parallel.•The setup is low-cost and require no custom parts.•The system can mimic a wide range of drug pharmacokinetics.