Successful treatment of acute experimental toxoplasmosis by spiramycin-loaded chitosan nanoparticles

Exp Parasitol. 2019 Sep:204:107717. doi: 10.1016/j.exppara.2019.107717. Epub 2019 Jun 20.

Abstract

Spiramycin-metronidazole and spiramycin-loaded chitosan (CS) nanoparticles (NPs) were tested in comparison with the current spiramycin treatment of T.gondii concerning tissue penetration and blood brain barrier (BBB) passage. Swiss Albino mice were inoculated intraperitoneally with 2500 T. gondii tachyzoites RH strain and were divided into experimental and control groups. The experimental groups orally received CS NPs, spiramycin, spiramycin-metronidazole, spiramycin-loaded CS NPs 400 mg/kg and spiramycin-loaded CS NPs 100 mg/kg. Drug efficacy was assessed by mice survival time, mortality rate, parasite load in different organs and morphological study of the tachyzoites movement by light microscope and the ultra-structure by SEM. The results revealed that the maximum survival time of more than 200 days with no mortality on the sacrifice day (8th) was observed in mice receiving spiramycin-loaded NPs. Spiramycin-loaded NPs showed the highest significant percent reduction of tachyzoites (about 90% reduction) in liver, spleen and brain as compared to the other used drugs denoting successful bypass of BBB. Light microscopy of the treated peritoneal tachyzoites showed sluggish tachyzoites movement while the NPs caused loss of their movement. SEM of the treated tachyzoites were more mutilated and some of them appeared rupturing in those receiving CS NPs and spiramycin-loaded NPs. In conclusion, spiramycin-loaded NPs showed the highest efficiency in the treatment of acute toxoplasmosis. The non-toxic nature and the anti-parasitic effect of both CS and spiramycin make the use of spiramycin-loaded CS NPs a potential material for treatment of human toxoplasmosis.

Keywords: CS NPs; Spiramycin; Spiramycin-loaded NPs; Spiramycin-metronidazole; Toxoplasma gondii.

MeSH terms

  • Acute Disease
  • Animals
  • Ascitic Fluid / parasitology
  • Biocompatible Materials
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Brain / parasitology
  • Chitosan
  • Coccidiostats / administration & dosage*
  • Drug Combinations
  • Drug Delivery Systems
  • Kaplan-Meier Estimate
  • Liver / parasitology
  • Male
  • Metronidazole / administration & dosage*
  • Mice
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Nanoparticles
  • Particle Size
  • Pilot Projects
  • Spiramycin / administration & dosage*
  • Spleen / parasitology
  • Survival Rate
  • Tablets
  • Toxoplasma / drug effects
  • Toxoplasma / ultrastructure
  • Toxoplasmosis, Animal / drug therapy*
  • Toxoplasmosis, Animal / mortality

Substances

  • Biocompatible Materials
  • Coccidiostats
  • Drug Combinations
  • Tablets
  • Metronidazole
  • Spiramycin
  • Chitosan