Evaluation of drug carrier hepatotoxicity using primary cell culture models

Nanomedicine. 2023 Feb:48:102651. doi: 10.1016/j.nano.2023.102651. Epub 2023 Jan 7.

Abstract

This study aims to establish a primary rat hepatocyte culture model to evaluate dose-dependent hepatotoxic effects of drug carriers (lipopolymer nanoparticles; LPNs) temporal. Primary rat hepatocyte cell cultures were used to determine half-maximal Inhibition Concentrations (IC50) of the drug-carrier library. Drug-carrier library, at concentrations <50 μg/mL, is benign to primary rat hepatocytes as determined using albumin and urea secretions. Albumin, as a hepatic biomarker, exhibited a more sensitive and faster outcome, compared to urea, for the determination of the IC50 value of LPNs. Temporal measurements of hepatic biomarkers including urea and albumin, and rigorous physicochemical (hydrodynamic diameter, surface charge, etc.) characterization, should be combined to evaluate the hepatotoxicity of drug carrier libraries in screens.

Keywords: Hepatotoxicity; In vitro culture; Lipopolymer nanoparticle (LPN); Nanotoxicity; Primary rat hepatocyte.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Albumins
  • Animals
  • Cells, Cultured
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Drug Carriers* / pharmacology
  • Hepatocytes
  • Primary Cell Culture
  • Rats
  • Urea / metabolism
  • Urea / pharmacology

Substances

  • Drug Carriers
  • Albumins
  • Urea