Synthesis and evaluation of isometamidium-alginate nanoparticles on equine mononuclear and red blood cells

Int J Biol Macromol. 2016 Nov:92:788-794. doi: 10.1016/j.ijbiomac.2016.07.084. Epub 2016 Jul 26.

Abstract

Isometamidium hydrochloride (ISMM) is an effective drug for the treatment of trypanosomosis, but it causes local and systemic toxicity. Isometamidium hydrochloride has limited therapeutic index and exhibit considerable variation in their prophylactic activities. We developed a trypanocidal nanoformulation using ISMM and polymers sodium alginate/gum acacia to enhance the efficacy of the drug at lower doses, while minimizing undesirable side effects. It was characterized by transmission electron microscopy and infrared spectroscopy for evaluation of size, morphology, functional groups, etc. In vitro cytotoxicity studies were performed by metabolic resazurin assay at different concentrations of isometamidium-loaded alginate/gum acacia nanoparticles using equine peripheral blood mononuclear cells. Hemolytic assay revealed significantly less toxicity compared to the conventional drug. The results demonstrate that the developed drug delivery module can be evaluated in suitable animal models to evaluate its potency.

Keywords: Cytotoxicity; Isometamidium; Polymers.

MeSH terms

  • Alginates / chemistry*
  • Animals
  • Cell Survival / drug effects
  • Cells, Cultured
  • Delayed-Action Preparations / chemical synthesis*
  • Delayed-Action Preparations / pharmacology
  • Drug Compounding
  • Erythrocytes / cytology
  • Erythrocytes / drug effects
  • Erythrocytes / metabolism
  • Glucuronic Acid / chemistry
  • Gum Arabic / chemistry*
  • Hexuronic Acids / chemistry
  • Horses
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Phenanthridines / pharmacology*
  • Trypanocidal Agents / pharmacology*

Substances

  • Alginates
  • Delayed-Action Preparations
  • Hexuronic Acids
  • Phenanthridines
  • Trypanocidal Agents
  • isometamidium chloride
  • Glucuronic Acid
  • Gum Arabic