In vitro Pharmacokinetic Cell Culture System that Simulates Physiologic Drug and Nanoparticle Exposure to Macrophages
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An in vitro dynamic pharmacokinetic (PK) cell culture system was developed to more precisely simulate physiologic nanoparticle/drug exposure.
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.
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.
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.
Key wordscell culture macrophage nanoparticles pharmacokinetic
Colony forming units
Dynamic light scattering
Human immunodeficiency virus
Transmission electron microscope
Ultra performance liquid chromatography-tandem mass spectrometry
Acknowledgments and Disclosures
Research reported in this publication was supported in part by 1R01AI129649-01A1 (NIAID) (JR); 1R56AI114298 (NIAID) (JR); University of Rochester Center for AIDS Research (CFAR) grant P30AI078498 (NIAID) (HK); and through a supplement to the University at Buffalo Pharmacology Specialty Laboratory, funded by UM1AI068634, UM1AI068636, and UM1AI106701 (NIAID)(GDM). HK was supported by Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grant 1T32GM099607 and UL1TR001412 (NCATS) (JR, HK). Research reported in this publication was supported in part by equipment donated by Waters Corporation. We acknowledge Dr. Martin Pavelka, University of Rochester, for the gernerous donation of M. Smegmatis. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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