In vitro Pharmacokinetic Cell Culture System that Simulates Physiologic Drug and Nanoparticle Exposure to Macrophages.
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.
['Kutscher|Hilliard L|HL|', 'Morse|Gene D|GD|', 'Prasad|Paras N|PN|', 'Reynolds|Jessica L|JL|']
D000900:Anti-Bacterial Agents D018929:Cell Culture Techniques D002460:Cell Line D004337:Drug Carriers D016503:Drug Delivery Systems D006801:Humans D008264:Macrophages D053758:Nanoparticles D010599:Pharmacokinetics D012293:Rifampin
pharmacokinetic cell culture nanoparticles macrophage