Evaluation of drug carrier hepatotoxicity using primary cell culture models

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

doi:10.1016/j.nano.2023.102651

Evaluation of drug carrier hepatotoxicity using primary cell culture models

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

Advanced Technologies for Preservation of Biological Systems

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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.

Original language	English (US)
Article number	102651
Journal	Nanomedicine: Nanotechnology, Biology, and Medicine
Volume	48
DOIs	https://doi.org/10.1016/j.nano.2023.102651
State	Published - 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

Keywords

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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title = "Evaluation of drug carrier hepatotoxicity using primary cell culture models",

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.",

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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: {\textcopyright} 2023",

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N2 - 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.

AB - 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.

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Evaluation of drug carrier hepatotoxicity using primary cell culture models

Abstract

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Evaluation of drug carrier hepatotoxicity using primary cell culture models

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

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ATP-Bio: NSF Engineering Research Center for Advanced Technologies for the Preservation of Biological Systems (ATP-Bio)

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