faezeh foroughi parvar

Toxoplasma gondii is one of the most common parasites worldwide. It is of great importance to identify new potential drugs that are effective and less harmful in pregnant women and newborns. We investigated nanoemulsion miltefosine (NEM) in treating experimental acute and chronic toxoplasmosis.

A combination of triacetin, Tween 80, and ethanol (1:2) was used for the development of NEM formulations. The size of NEM was calculated to be 17.463 nm by DLS and TEM. To investigate the performance of miltefosine (MLF), NEM, sulfadiazine (SDZ), and pyrimethamine (PYR) (positive control) in vivo, acute toxoplasmosis was induced in mice by an intraperitoneal injection of RH strain tachyzoites. After five days, the mice were examined for the number and condition of tachyzoites and histopathological changes in the liver and spleen. Chronic toxoplasmosis was investigated in rats and the number and size of brain cysts along with histopathological changes were assessed in different groups.

The results of the in vivo assessment of drugs in acute toxoplasmosis showed the following order regarding a decrease in the number of tachyzoites and an increase in survival rate: SDZ&PYR > NEM > MLF. The effects of drugs on chronic toxoplasmosis showed a significant effect of NEM (50%) on reducing the number of cysts compared to SDZ&PYR (10%) and MLF (12%) and reducing the size of NEM brain cysts (21%) compared to SDZ&PYR (5 %) and MLF (8%).

Increasing the penetration of NEM through the blood-brain barrier (BBB) and subsequently reducing the number and size of T. gondii tissue cysts is a promising new drug in treating chronic toxoplasmosis.

Toxoplasma gondii is a common parasite in the world. Pharmaceutical options for toxoplasmosis treatment are limited. Several studies have been conducted on the anti-infectious properties of miltefosine (MLF). We investigated the effectiveness of nanoemulsion miltefosine (NEM) in tachyzoites of T. gondii, RH strain. Various NEM formulations were designed considering pseudo-ternary phase diagrams. Physicochemical properties of the developed nanoemulsions (NEs), including pH, polydispersity index (PDI), droplet size, and refractive index (RI) were evaluated. The considered formulation was analyzed for dilution and stability tests. MTT assay was performed on Vero cells for calculation CC50 and on Vero cells with RH strain tachyzoite for calculation IC50. Sulfadiazine (SDZ) and pyrimethamine (PYR) were positive controls. The trypan blue method was used to investigate the effect of drugs (NEM, MLF, SDZ, PYR) in reducing the number of infected Vero cells and reducing the intracellular proliferation of tachyzoites. Next, the viability of tachyzoites was measured in the tube in the direct vicinity of different drug concentrations. The final particle size of NEM was calculated to be 17.463 nm by DLS and TEM. The CC50 of NEM (75.7 µg/mL) indicated lower toxicity than the other drugs. IC50 obtained by trypan blue, MTT, and test tube methods showed that NEM (28.43 µg/mL) has a suitable IC50 against Toxoplasma tachyzoites. The calculated selectivity index (SI) demonstrated that NEM (SI=2.66) is a more suitable drug candidate than the MLF and positive controls. The trypan blue assay indicated the excellent reduction effect of NEM on T. gondii intracellular proliferation rate and the number of infected cells.