We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
In vitro Pharmacokinetic Cell Culture System that Simulates Physiologic Drug and Nanoparticle Exposure to Macrophages.
- Authors
Kutscher, Hilliard L.; Morse, Gene D.; Prasad, Paras N.; Reynolds, Jessica L.
- 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.
- Subjects
PHARMACOKINETICS; NANOMEDICINE; CELL culture; MACROPHAGES; COMPUTER simulation; ANTI-infective agents
- Publication
Pharmaceutical Research, 2019, Vol 36, Issue 3, p1
- ISSN
0724-8741
- Publication type
Article
- DOI
10.1007/s11095-019-2576-9