Self-assembled FGF21 nanoparticles alleviate drug-induced acute liver injury

Zhiwei Huang; Hengcai Wang; Changju Chun; Xinze Li; Shihao Xu; Yingzheng Zhao

doi:10.3389/fphar.2022.1084799

Self-assembled FGF21 nanoparticles alleviate drug-induced acute liver injury

Front Pharmacol. 2023 Jan 10:13:1084799. doi: 10.3389/fphar.2022.1084799. eCollection 2022.

Authors

Zhiwei Huang^{1

2}, Hengcai Wang¹, Changju Chun², Xinze Li³, Shihao Xu⁴, Yingzheng Zhao¹

Affiliations

¹ Department of pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
² College of Pharmacy, Research Institute of Pharmaceutical Sciences, Chonnam National University, Gwangju, South Korea.
³ Department of Emergency, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁴ Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Abstract

Acetaminophen (N-acetyl-p-aminophenol, APAP) is a common antipyretic agent and analgesic. An overdose of APAP can result in acute liver injury (ALI). Oxidative stress and inflammation are central to liver injury. N-acetylcysteine (NAC), a precursor of glutathione, is used commonly in clinical settings. However, the window of NAC treatment is limited, and more efficacious alternatives must be found. Endogenous cytokines such as fibroblast growth factor (FGF) 21 can improve mitochondrial function while decreasing intracellular oxidative stress and inflammatory responses, thereby exhibiting antioxidant-like effects. In this study, self-assembled nanoparticles comprising chitosan and heparin (CH) were developed to deliver FGF21 (CH-FGF21) to achieve the sustained release of FGF21 and optimize the in vivo distribution of FGF21. CH-FGF21 attenuated the oxidative damage and intracellular inflammation caused by APAP to hepatocytes effectively. In a murine model of APAP-induced hepatotoxicity, CH-FGF21 could alleviate ALI progression and promote the recovery of liver function. These findings demonstrated that a simple assembly of CH nanoparticles carrying FGF21 could be applied for the treatment of liver diseases.

Keywords: fibroblast growth factor 21; inflammation; liver-targeted therapy; nanoparticles; oxidative stress.

Grants and funding

This research was supported by Zhejiang Provincial Natural Science Foundation (Key Program Grant No. LZ23H040001), Wenzhou Scientific and Technological Innovation Project (Grant No. ZY2021019), Wenzhou Innovative Technology Project for High-level Talents (YZ), Zhejiang Provincial Medical and Health Science and Technology Program (Grant No. 2023KY143), and Basic Scientific Research Project in Wenzhou Science and Technology Bureau (Grant No. Y20220087).