Decreasing acute toxicity and suppressing colorectal carcinoma using Sorafenib-loaded nanoparticles

Pharm Dev Technol. 2020 Jun;25(5):556-565. doi: 10.1080/10837450.2020.1718704. Epub 2020 Feb 2.

Abstract

Objective: A polymer-based nanoparticle was constructed to target sorafenib delivery to colorectal carcinoma cells and decrease the side effects of the drug.Methods: Sorafenib-loaded nanoparticles (S-NPs) based on PEG-PLGA were prepared using a double emulsion solvent evaporation method. The properties of S-NPs were evaluated and then their effects on the viability of colorectal cancer cells and normal human cells were assessed. The mechanism of S-NP internalization was explored using cellular uptake assays and in vitro fluorescence confocal imaging. Acute toxicity of sorafenib on its own or within S-NPs was assessed in mice.Results: S-NPs showed high drug loading and entrapment efficiencies, they did not cause extensive hemolysis, and they efficiently inhibited growth of colorectal cancer cell lines and human umbilical vein endothelial cells. S-NPs showed lower acute toxicity than the free drug.Conclusions: Loading sorafenib into nanoparticles can enhance its uptake by colorectal cancer cells and decrease its acute toxicity.

Keywords: Sorafenib; acute toxicity; cellular uptake; colorectal cancer; nanoparticles.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colorectal Neoplasms / pathology
  • Drug Carriers / chemistry*
  • Drug Compounding
  • Endocytosis / drug effects
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lethal Dose 50
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Particle Size
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemistry*
  • Sorafenib / administration & dosage
  • Sorafenib / chemistry
  • Sorafenib / pharmacology*
  • Sorafenib / toxicity
  • Toxicity Tests, Acute

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Polyesters
  • polyethylene glycol-poly(lactide-co-glycolide)
  • Polyethylene Glycols
  • Sorafenib