Self-assembly drug-albumin nanocomposites for nonalcoholic fatty liver disease treatment

  • Int J Biol Macromol. 2022 Aug 1;214:697-707. doi: 10.1016/j.ijbiomac.2022.06.167.
Weihong Jing  1 Mingyue Jiang  1 Xiaoxue Fu  1 Jiaxin Yang  1 Lu Chen  1 Feng Leng  1 Ping Xu  1 Wenyan Huang  1 Chao Yu  2 Zhangyou Yang  3
Affiliations
  • 1. Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China.
  • 2. Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: [email protected].
  • 3. Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: [email protected].
Abstract

Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease closely related to obesity, which has become a global health problem. However, current pharmacological therapies for NAFLD are limited by potential side effects, low effectiveness and poor aqueous solubility. Herein, we designed functionalized drug-albumin nanocomposites (BAM15@BSA NPs), which were prepared by self-assembly of the anti-obesity small-molecule drug (BAM15) and bovine serum albumin (BSA), for treatment of NAFLD. The proposed BAM15@BSA NPs not only improve aqueous solubility and half-life of BAM15 but also exhibit hepatic-targeted capacity and an increased therapeutic efficacy. In vitro experiments revealed that BAM15@BSA NPs possessed excellent biocompatibility, and improved resistance to adipogenesis and reduced lipid accumulation in human hepatocellular carcinoma cells. In vivo, BAM15@BSA NPs showed liver targeting ability and powerful anti-obesity effects without altering body temperature or affecting food intake, and could effectively alleviate hepatic steatosis and improve therapeutic efficacy for NAFLD treatment. The above findings demonstrated that BAM15@BSA NPs potentially served as a safe and effective drug for NAFLD treatment.

Keywords
BAM15; Drug-albumin nanocomposites; Nonalcoholic fatty liver disease; Obesity; Self-assembly.
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