Effectiveness of Miltefosine Nanoemulsion Concerning the Treatment of Acute and Chronic Toxoplasmosis: In Vivo Study

Gholam Reza  Valizadeh; Mohammad Mahdi  Mahboubian; Amir Hossein  Maghsoud; Fatemeh  Mirzaei; Seyedmousa Motavalli Haghi; Faezeh  Foroughi Parvar; Mohammad  Fallah

doi:10.18502/ijpa.v19i3.16389

Gholam Reza Valizadeh Department of Parasitology and Mycology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Mohammad Mahdi Mahboubian Department of Pharmaceutics, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
Amir Hossein Maghsoud Department of Parasitology and Mycology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Fatemeh Mirzaei Department of Anatomy, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Seyedmousa Motavalli Haghi Department of Parasitology and Mycology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Faezeh Foroughi Parvar Department of Parasitology and Mycology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
Mohammad Fallah Department of Parasitology and Mycology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

DOI: https://doi.org/10.18502/ijpa.v19i3.16389

Keywords: Acute; Chronic; In vivo; Miltefosine; Toxoplasmosis

Abstract

Background: 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.

Methods: 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.

Results: 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%).

Conclusion: 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.