Evaluation of drug carrier hepatotoxicity using primary cell culture models

Güneş Kibar, Subhadeep Dutta, Kaushal Rege, O. Berk Usta

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number102651
JournalNanomedicine: Nanotechnology, Biology, and Medicine
StatePublished - Feb 2023

Bibliographical note

Funding Information:
Acknowledgments and funding support: This research was supported by grants from the National Institutes of Health (NIH 1R21GM136002 and NIH 5R01HL145031 ), the National Science Foundation (NSF Engineering Research Center, Award # 1941543 ), and a Massachusetts General Hospital (MGH) Executive Committee on Research (ECOR) Interim Support Fund at Dr. Usta's lab. We also acknowledge the support and use of facilities at the Morphology and Imaging Shared Facility, and Regenerative Medicine Shared Facility provided at the Shriners' Children - Boston. We also acknowledge the Turkish Fulbright Commission for a Fulbright Postdoctoral Scholarship and the Scientific and Technological Research Council of Turkey (Tubitak 2219 Award #1059B191801017) for Dr. Gunes Kibar. We are also grateful to the NIH (Grant R41 TR003247 to Synergyan, LLC and KR) for partially supporting this study at Dr. Rege's lab. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the NSF.

Publisher Copyright:
© 2023


  • Hepatotoxicity
  • In vitro culture
  • Lipopolymer nanoparticle (LPN)
  • Nanotoxicity
  • Primary rat hepatocyte

PubMed: MeSH publication types

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


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