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Pharm Res. 2019 Feb 1;36(3):44. doi: 10.1007/s11095-019-2576-9.

In vitro Pharmacokinetic Cell Culture System that Simulates Physiologic Drug and Nanoparticle Exposure to Macrophages.

Author information

1
Translational Pharmacology Research Core, NYS Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, Buffalo, New York, 14203, USA.
2
Institute for Lasers, Photonics and Biophotonics, University at Buffalo, Buffalo, New York, 14260, USA.
3
Department of Anesthesiology, University at Buffalo, Buffalo, New York, 14203, USA.
4
Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, 14214, USA.
5
Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, 14203, USA. Jlr8@buffalo.edu.

Abstract

PURPOSE:

An in vitro dynamic pharmacokinetic (PK) cell culture system was developed to more precisely simulate physiologic nanoparticle/drug exposure.

METHODS:

A dynamic PK cell culture system was developed to more closely reflect physiologic nanoparticle/drug concentrations that are changing with time. Macrophages were cultured in standard static and PK cell culture systems with rifampin (RIF; 5 μg/ml) or β-glucan, chitosan coated, poly(lactic-co-glycolic) acid (GLU-CS-PLGA) nanoparticles (RIF equivalent 5 μg/ml) for 6 h. Intracellular RIF concentrations were measured by UPLC/MS. Antimicrobial activity against M. smegmatis was tested in both PK and static systems.

RESULTS:

The dynamic PK cell culture system mimics a one-compartment elimination pharmacokinetic profile to properly mimic in vivo extracellular exposure. GLU-CS-PLGA nanoparticles increased intracellular RIF concentration by 37% compared to free drug in the dynamic cell culture system. GLU-CS-PLGA nanoparticles decreased M. smegmatis colony forming units compared to free drug in the dynamic cell culture system.

CONCLUSIONS:

The PK cell culture system developed herein enables more precise simulation of human PK exposure (i.e., drug dosing and drug elimination curves) based on previously obtained PK parameters.

KEYWORDS:

cell culture; macrophage; nanoparticles; pharmacokinetic

PMID:
30710170
PMCID:
PMC6547366
DOI:
10.1007/s11095-019-2576-9
[Indexed for MEDLINE]
Free PMC Article

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