Mefloquine loaded niosomes as a promising approach for the treatment of acute and chronic toxoplasmosis

Abstract

Toxoplasmosis is a disease with a worldwide distribution and significant morbidity and mortality. In search of effective treatment, mefloquine (MQ) was repurposed and loaded with niosomes to treat acute and chronic phases of toxoplasmosis in experimental mice. Mice were orally inoculated with 20 cysts of Toxoplasma gondii (ME 49 strain) for the acute model of infection and 10 cysts for the chronic model of infection. Infected mice were dosed with MQ solution or MQ-niosomes at 50 mg/kg/day, starting from the second day post-infection (PI) (acute model) or the fifth week PI (chronic model), and this was continued for six consecutive days. The effects of MQ solution and MQ-niosomes were compared with a pyrimethamine/sulfadiazine (PYR/SDZ) dosing combination as mortality rates, brain cyst number, inflammatory score, and immunohistochemical studies that included an estimation of apoptotic cells (TUNEL assays). In the acute infection model, MQ solution and MQ-niosomes significantly reduced the mortality rate from 45% to 25 and 10%, respectively, compared with infected untreated controls, and decreased the number of brain cysts by 51.5% and 66.9%, respectively. In the chronic infection model, cyst reduction reached 80.9% and 12.3% for MQ solution and MQ-niosomes treatments, respectively. MQ-niosomes significantly decreased inflammation induced by acute or chronic T. gondii infection. Additionally, immunohistochemical analysis revealed that MQ solution and MQ-niosomes significantly increased the number of TUNEL-positive cells in brain tissue, indicative of induction of apoptosis. Collectively, these results indicate that MQ-niosomes may provide a useful delivery strategy to treat both acute and chronic toxoplasmosis.