In Vitro Pharmacokinetic Cell Culture System That Simulates Physiologic Drug and Nanoparticle Exposure to Macrophages

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2019 Feb 3

PMID 30710170

Citations 5

Authors

Hilliard L Kutscher

Gene D Morse

Paras N Prasad

Jessica L Reynolds

Affiliations

Soon will be listed here.

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.

Citing Articles

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