Rapamycin-Loaded mPEG-PLGA Nanoparticles Ameliorate Hepatic Steatosis and Liver Injury in Non-alcoholic Fatty Liver Disease

Ruifang Zhao; Meilin Zhu; Shuang Zhou; Weiyue Feng; Hanqing Chen

doi:10.3389/fchem.2020.00407

Rapamycin-Loaded mPEG-PLGA Nanoparticles Ameliorate Hepatic Steatosis and Liver Injury in Non-alcoholic Fatty Liver Disease

Front Chem. 2020 May 28:8:407. doi: 10.3389/fchem.2020.00407. eCollection 2020.

Authors

Ruifang Zhao^{1

2}, Meilin Zhu^{3

4}, Shuang Zhou³, Weiyue Feng³, Hanqing Chen^{1

3}

Affiliations

¹ Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
² National Center for Nanoscience and Technology, Beijing, China.
³ CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences (CAS), Beijing, China.
⁴ Institute of Physical Science and Information Technology, Anhui University, Hefei, China.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and liver injury, and is the leading cause of chronic liver disease worldwide. There is an urgent need to develop novel pathophysiology-oriented therapy in human. Rapamycin (RAPA) has been recognized as a promising drug for alleviating hepatic steatosis on NAFLD, but the poorly water-soluble properties and side effects of RAPA limit their clinical use. In this study, we aimed to investigate the in vitro and in vivo therapeutic efficacy of biodegradable mPEG-PLGA polymers loaded with RAPA (NP-RAPA) on NAFLD. NP-RAPA were prepared by a green process using an emulsion/solvent evaporation method, the therapeutic efficacy on NAFLD were investigated on HepG2 cells incubated with oleic acid (OA) and in the livers of mice with NAFLD induced by high-fat diet (HFD). Compared with free RAPA, NP-RAPA significantly reduced lipid accumulation in HepG2 cells, and obviously ameliorated hepatic steatosis and liver injury in mice though enhancing the therapeutic efficacy of RAPA through reducing SREBP-1c-dependent de novo lipogenesis (DNL) and promoting PPARα-mediated fatty acid oxidation. This study suggests that mPEG-PLGA can be used as the potential therapeutic strategy and novel drug delivery for improving the efficacy of rapamycin for treatment of NAFLD.

Keywords: SREBP-1c; de novo lipogenesis; fatty acid oxidation; hepatic steatosis; mPEG-PLGA; non-alcoholic fatty liver disease; rapamycin.