Preparation of microspheres encapsulating sorafenib and catalase and their application in rabbit VX2 liver tumor

Biomed Pharmacother. 2020 Sep:129:110512. doi: 10.1016/j.biopha.2020.110512. Epub 2020 Jul 10.

Abstract

Background: Transcatheter arterial chemoembolization (TACE) is extensively used in the treatment of advanced hepatocellular carcinoma (HCC). However, the efficacy of TACE is usually limited to secondary tumor hypoxia and hypoxia-related tumor angiogenesis.

Methods: In this study, poly(lactic-co-glycolic acid) (PLGA) microspheres (SOR-CAT-PLGA MSs) encapsulating sorafenib (SOR) and catalase (CAT) were prepared by double-emulsion solvent diffusion method. Sorafenib inhibits tumor angiogenesis, and catalase decomposes hydrogen peroxide (H2O2) to generate oxygen in the tumor.

Results: In vitro and in vivo, SOR -CAT-PLGA MSs could significantly improve the efficacy of hepatic artery embolization in the treatment of rabbit VX2 liver tumors, regulate tumor hypoxia and immunosuppressive microenvironment, then achieved near-complete and rapid necrosis of liver tumors.

Conclusions: The application of new SOR -CAT-PLGA MSs in hepatic artery chemoembolization of rabbit VX2 liver tumor is a promising approach to improve the therapeutic effect of liver tumors and has a broad clinical application prospect.

Keywords: Catalase; Liver tumor; Microspheres; Sorafenib; Transcatheter arterial chemoembolization.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / chemistry
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Catalase / chemistry
  • Catalase / pharmacology*
  • Cell Line, Tumor
  • Chemoembolization, Therapeutic*
  • Drug Compounding
  • Female
  • Hydrogen Peroxide / metabolism
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Male
  • Microspheres
  • Necrosis
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
  • Rabbits
  • Sorafenib / chemistry
  • Sorafenib / pharmacology*
  • Tumor Hypoxia
  • Tumor Microenvironment

Substances

  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Sorafenib
  • Hydrogen Peroxide
  • Catalase