Evaluation of the efficacy of Chitosan nanoparticles based on Rosuvastatin in the treatment of acute toxoplasmosis: An In vitro and In vivo study

Microb Pathog. 2024 Oct:195:106897. doi: 10.1016/j.micpath.2024.106897. Epub 2024 Aug 28.

Abstract

Toxoplasma gondii (T.gondii) is an obligate intracellular protozoan that infects warm-blooded animals and has a global distribution. Acute toxoplasmosis is commonly reported in patients with acquired/congenital toxoplasmosis and immune deficiency. New methods are needed to prevent the sideffects of classical treatment. In this study, Rosuvastatin loaded chitosan nanoparticle (CH-NP-ROS) were synthesized and zeta potential and size were determined, and an MTT assay was performed to evaluate the cell toxicity on Macrophage cells (MQ) and anti-Toxoplasma activity using Trypan-blue staining by different concentrations of Rosuvastatin (ROS), and Rosuvastatin loaded chitosan nanoparticle (CH-NP-ROS). The cell viability assay demonstrated that CH-NP-ROS had lower cell toxicity (<15 %) compared to ROS (<30 %). Statistical analysis showed that CH-NP-ROS significantly killed 98.950 ± 1.344; P < 0.05) of Toxoplasma gondii tachyzoites. In vivo results of perituneal fluid showed that CH-NP significantly reduced the parasite load in the CH-NP-ROS group, compared to that in negative control group (P < 0.001). Growth inhibition rates of tachyzoites in mice receiving free ROS and CH-NP-ROS (injection and oral form) were found to be 166.125 + 4.066, 118.750 + 4.596 and 124.875 + 2.652, respectively, compared to mice in Sulfadiazine/Pyrimethamine treated group (positive control). In the infected untreated mice (control +), the mean tachyzoite counts per oil immersion field in the spleen was 8.25 respectively. The mean survival time in all the groups treated with ROS and CH-NP-ROS was longer than that in the negative control group Therefore, nanoformulation is a promising approach for the delivery and is safe for using therapeutic effects in acute toxoplasmosis.

Keywords: Acute toxoplasmosis; BALB/C mice; Chitosan nanoparticles; Cytotoxicity; Rosuvastatin; Rosuvastatin loaded.

MeSH terms

  • Animals
  • Antiprotozoal Agents / pharmacology
  • Antiprotozoal Agents / therapeutic use
  • Cell Survival / drug effects
  • Chitosan*
  • Disease Models, Animal
  • Drug Carriers
  • Female
  • Macrophages / drug effects
  • Macrophages / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles* / chemistry
  • Parasite Load
  • Rosuvastatin Calcium* / administration & dosage
  • Rosuvastatin Calcium* / pharmacology
  • Rosuvastatin Calcium* / therapeutic use
  • Toxoplasma* / drug effects
  • Toxoplasmosis* / drug therapy
  • Toxoplasmosis* / parasitology
  • Toxoplasmosis, Animal / drug therapy
  • Toxoplasmosis, Animal / parasitology

Substances

  • Chitosan
  • Rosuvastatin Calcium
  • Antiprotozoal Agents
  • Drug Carriers