Toxoplasma gondii infection has a worldwide distribution. Pyrimethamine (PYR) is the most effective drug for treatment of toxoplasmosis. Unfortunately, it has low oral bioavailability which requires an increase in the dose that results in increased its side effects. Nanostructures showed promising potential to overcome this problem. This study aimed to evaluate the effect of intraperitoneal injection (IP) of PYR-loaded niosomes compared to PYR in the treatment of acute toxoplasmosis in experimentally infected mice. The study employed 240 mice that were divided into groups. Group I included Ia (20 uninfected untreated), Ib (20 infected untreated), Ic (non-infected and injected with placebo niosomes) and Id (20 non-infected mice injected with dimethyl sulfoxide). Groups II and III (a & b/each, 40 mice/each) were treated with PYR and PYR-loaded niosomes respectively in doses of 5 or 10 mg/kg/day for four successive days. Then all mice were sacrificed and their peritoneal fluids were examined by the scanning electron microscopy. Livers, spleens and brains were used for parasite count and for histopathological examination. This study showed that the niosomes improved the efficacy of PYR in the treatment of acute toxoplasmosis in mice. It was evidenced by increased the survival rate, decreased tachyzoites count, morphological changes of the tachyzoites and decreased inflammation. Niosomal PYR was effective at low dose with its efficacy being even greater than that of the solution even at high dose. It was concluded that PYR-niosomes formulation is a powerful alternative for reduction of PYR dose and its side effects. K e y w o r d sToxoplasma gondii.

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Chronic toxoplasmosis is considered as one of the major neglected tropical diseases. Although there are many treatment modalities for acute toxoplasmosis, there is still insufficient knowledge about a safe effective treatment for chronic toxoplasmosis till now. However, guanabenz has shown a promising result for treatment of Toxoplasma gondii infection although it could not completely eradicate all brain tissue cysts. This study was designed to test the effect of guanabenz-loaded polyethylene glycol poly lactic-co-glycolic acid (PEG PLGA) nanoparticles on mortality rate of mice infected with chronic toxoplasmosis. The study was conducted in Tanta University, Medical Parasitology laboratory on 160 mice that were divided as follows: Group I (five subgroups each of 20 mice): Ia: non-infected non-treated, Ib: infected untreated, Ic: non-infected mice given nanoparticles alone, Id: infected mice given nanoparticles alone and Ie: infected mice treated by pyrimethamine (4 mg/kg) and sulfadiazine (100 mg/kg). Group II (three subgroups each of 20 mice): IIa: Infected and treated mice with guanabenz alone (5mg/kg/day), IIb: Infected and treated mice with guanabenz-loaded nanoparticles by full dose and IIc: Infected and treated mice with guanabenz-loaded nanoparticles by the half dose (2.5 mg/kg/day). The drugs were given on day 25 post-infection for 19 successive days. On the 20th day the mortality rate was calculated in different subgroups. The data were processed statistically. The Results showed that although guanabenz-loaded nanoparticles were given by intraperitoneal injection which carries much more infection hazards and stress on the mice, it caused less mortality rate in mice than subgroup Ie which was given pyrimethamine and sulfadiazine combination therapy orally, however this was of no statistically significant difference. It could be concluded that guanabenz-loaded PEG-PLGA nanoparticles cause no increase in the mortality rate of mice infected with chronic toxoplasmosis.