International Journal of Nanomedicine (Nov 2018)
Curcumin nanoemulsion as a novel chemical for the treatment of acute and chronic toxoplasmosis in mice
Abstract
Sanaz Jafarpour Azami,1,* Aref Teimouri,1,2,* Hossein Keshavarz,1 Amir Amani,3,4 Fariba Esmaeili,3 Hamid Hasanpour,1,5 Samira Elikaee,1 Hamid Salehiniya,6 Saeedeh Shojaee1 1Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; 2Students Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 4Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran; 5Department of Medical Parasitology and Mycology, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran; 6Department of Public Health, School of Health, Zabol University of Medical Sciences, Zabol, Iran *These authors contributed equally to this work Background: The aim of this study was to prepare curcumin nanoemulsion (CR-NE) to solve the problems associated with poor water solubility and low bioavailability of CR and to test its efficiency in the treatment of acute and chronic toxoplasmosis in mouse models. Materials and methods: CR-NE 1% was prepared using spontaneous emulsification by soybean as oil phase; a mixture of Tween 80 and Tween 85 as surfactant; ethanol as cosurfactant and distilled water. Particle size and zeta potential of NE were assessed using Nano-ZS90 dynamic light scattering. Stability testing of NE was assessed after storage for 2 months at room temperature. In vivo experiments were carried out using 50 BALB/c mice inoculated with virulent RH strain (type I) and 50 BALB/c mice inoculated with avirulent Tehran strain (type II) of Toxoplasma gondii and treated with CR-NE (1% w/v), CR suspension (CR-S, 1% w/v), and NE without CR (NE-no CR). Results: The mean particle size and zeta potential of CR-NE included 215.66±16.8 nm and -29.46±2.65 mV, respectively, and were stable in particle size after a three freeze–thaw cycle. In acute phase experiment, the survival time of mice infected with RH strain of T. gondii and treated with CR-NE extended from 8 to 10 days postinoculation. The differences were statistically significant between the survival time of mice in CR-NE-treated group compared with negative control group (P<0.001). Furthermore, CR-NE significantly decreased the mean counts of peritoneum tachyzoites from 5,962.5±666 in negative control group to 627.5±73 in CR-NE-treated mice (P<0.001). Growth inhibition rates of tachyzoites in peritoneum of mice receiving CR-NE, CR-S, and NE-no CR included 90%, 21%, and 11%, respectively, compared with negative control group. In chronic phase experiment, the average number and size of tissue cysts significantly decreased to 17.2±15.6 and 31.5±6.26 µm, respectively, in mice inoculated with bradyzoites of T. gondii Tehran strain and treated with CR-NE compared with that in negative control group (P<0.001). Decrease of cyst numbers was verified by downregulation of BAG1 in treatment groups compared with negative control group with a minimum relative expression in CR-NE (1.12±0.28), CR-S (11.76±0.87), and NE-no CR (14.67±0.77), respectively, (P<0.001). Conclusion: Results from the current study showed the potential of CR-S and CR-NE in treatment of acute and chronic toxoplasmosis in mouse models for the first time. However, CR-NE was more efficient than CR-S, and it seems that CR-NE has a potential formula for the treatment of acute and chronic toxoplasmosis, especially in those with latent bradyzoites in brain. Keywords: curcumin nanoemulsion, curcumin suspension, Toxoplasma gondii RH strain, Toxoplasma gondii Tehran strain, soybean oil, blood–brain barrier, spontaneous emulsification
