Co-delivery of spiramycin and curcumin nanoemulsions for treating acute (RH strain) and chronic (Tehran strain) toxoplasmosis in BALB/c mice

This study aimed to develop and evaluate a nanoemulsion containing spiramycin and curcumin (NE-CS) to enhance these compounds' bioavailability and efficacy against acute and chronic toxoplasmosis in mice. Nanoemulsion containing spiramycin and curcumin (NE-CS), spiramycin nanoemulsion (NE-Spi), and a nanoemulsion without the drug (NE) were prepared via spontaneous emulsification and characterized for particle size and zeta potential. Their in vitro activity was tested against tachyzoites of T. gondii, RH strain, at different concentrations (250, 125, 62.5, and 31.25 µg/ml) and time points (30, 60, 90, and 120 min). In vivo, BALB/c mice infected with RH and Tehran strains were treated with NE-CS (25 mg/kg/day curcumin + 50 mg/kg/day spiramycin), NE-Spi (50 mg/kg/day), S-Spi, and NE, with infected/untreated mice as controls. Survival time, tachyzoite counts in peritoneal fluid (acute phase), and number and size of tissue cysts (chronic phase) were assessed microscopically. NE-CS significantly decreased the intracellular multiplication of T. gondii tachyzoites (5 ± 2.78 × 10⁴) compared with that of the infected/untreated group (3509 ± 435.39 × 10⁴). Oral administration of NE-CS improved therapeutic outcomes in vivo, prolonged survival time in mice (13 days), reduced parasitemia, and decreased both the number (43 ± 5.78) and size (4 ± 1.11 µm) of brain cysts compared to the infected/untreated group (380 ± 17.22 and 112.8 ± 8.28 µm, respectively). This study demonstrated the in vitro efficiency of nanoemulsion co-delivery of curcumin and spiramycin for increasing tachyzoite death, and indicated the possibility of NE-CS and NE-Spi for treating acute and chronic toxoplasmosis in murine models. However, further investigations are needed to confirm their safety and effectiveness across broader models.