Cytotoxicity and genotoxicity of a trypanocidal drug quinapyramine sulfate loaded-sodium alginate nanoparticles in mammalian cells

Int J Biol Macromol. 2016 Jul:88:146-55. doi: 10.1016/j.ijbiomac.2016.03.034. Epub 2016 Mar 18.

Abstract

We synthesized quinapyramine sulfate loaded-sodium alginate nanoparticles (QS-NPs) to reduce undesirable toxic effects of QS against the parasite Trypanosoma evansi, a causative agent of trypanosomosis. To determine the safety of the formulated nanoparticles, biocompatibility of QS-NPs was determined using Vero, Hela cell lines and horse erythrocytes in a dose-dependent manner. Our experiments unveiled a concentration-dependent safety/cytotoxicity (metabolic activity), genotoxicity (DNA damage, chromosomal aberrations), production of reactive oxygen species and hemolysis in QS-NPs treated cells. Annexin-V propidium iodide (PI) staining showed no massive apoptosis or necrosis. However, at very high doses (more than 300 times than the effective doses), we observed more toxicity in QS-NPs treated cells as compared to QS treated cells. QS-NPs were safe at effective trypanocidal doses and even at doses several times higher than the effective dose.

Keywords: Cytotoxicity; Genotoxicity; Nanomedicine; Oxidative stress; Trypanosoma.

MeSH terms

  • Alginates / chemistry*
  • Animals
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Chromosome Aberrations / drug effects
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Drug Carriers*
  • Drug Compounding
  • Erythrocytes / drug effects
  • Glucuronic Acid / chemistry
  • HeLa Cells
  • Hemolysis / drug effects
  • Hexuronic Acids / chemistry
  • Horses
  • Humans
  • Nanoparticles / chemistry
  • Nanoparticles / toxicity*
  • Nanoparticles / ultrastructure
  • Quinolinium Compounds / chemistry
  • Quinolinium Compounds / toxicity*
  • Reactive Oxygen Species / metabolism
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / toxicity*
  • Vero Cells

Substances

  • Alginates
  • Drug Carriers
  • Hexuronic Acids
  • Quinolinium Compounds
  • Reactive Oxygen Species
  • Trypanocidal Agents
  • Glucuronic Acid
  • quinapyramine