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Pharmaceutical Research

, 36:44 | Cite as

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

  • Hilliard L. Kutscher
  • Gene D. Morse
  • Paras N. Prasad
  • Jessica L. ReynoldsEmail author
Research Paper
  • 54 Downloads
Part of the following topical collections:
  1. Nanomedicine for Infectious Diseases

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.

Key words

cell culture macrophage nanoparticles pharmacokinetic 

Abbreviations

CFU

Colony forming units

CS

Chitosan

DAPI

4′,6-diamidino-2-phenylindole

DCM

Dichloromethane

DLS

Dynamic light scattering

GLU

1,3 β-glucan

HIV

Human immunodeficiency virus

PK

Pharmacokinetic

PLGA

Poly(lactic-co-glycolic) acid

PVA

Poly(vinyl alcohol)

RIF

Rifampin

RifP

Rifapentine

TB

Tuberculosis

TEM

Transmission electron microscope

UPLC-MS/MS

Ultra performance liquid chromatography-tandem mass spectrometry

Notes

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.

Supplementary material

11095_2019_2576_MOESM1_ESM.docx (1.2 mb)
ESM 1 (DOCX 1276 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hilliard L. Kutscher
    • 1
    • 2
    • 3
  • Gene D. Morse
    • 1
    • 4
  • Paras N. Prasad
    • 2
  • Jessica L. Reynolds
    • 5
    Email author
  1. 1.Translational Pharmacology Research Core, NYS Center of Excellence in Bioinformatics and Life SciencesUniversity at BuffaloBuffaloUSA
  2. 2.Institute for Lasers, Photonics and BiophotonicsUniversity at BuffaloBuffaloUSA
  3. 3.Department of AnesthesiologyUniversity at BuffaloBuffaloUSA
  4. 4.Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical SciencesUniversity at BuffaloBuffaloUSA
  5. 5.Department of Medicine, Jacobs School of Medicine and Biomedical SciencesUniversity at BuffaloBuffaloUSA

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