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

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.

Niosomes for enhanced activity of praziquantel against Schistosoma mansoni: in vivo and in vitro evaluation.

Praziquantel (PZQ) is recommended by the WHO as the first line in treatment of schistosomiasis. Unfortunately, it exhibits low oral bioavailability which can compromise its efficacy. Nanostructures showed promising potential to overcome this problem. Accordingly, the aim of this study was to investigate the effect of niosomal encapsulation of PZQ on its activity on Schistosoma mansoni in vitro and in vivo. PZQ was encapsulated in niosomal formulation comprising span 60, cholesterol with peceol being included as absorption enhancer. The in vitro work determined the schistosomicidal activity and morphological changes after incubation with drug solution or PZQ-niosomes. The in vivo study utilized infected mice which received PZQ orally as solution or as niosomes. The activity was assessed by monitoring egg and worm count in addition to histopathological and immunohistochemical studies. The in vitro studies revealed that niosomes alone caused a 30% death of adult parasites and caused completely coiled body, destruction, and peeling of tubercles and spines, with flattening and effacement of gynecophoric canal, blebbing with niosomes vesicles attached to it. Niosomes containing PZQ at a concentration of 0.001 µg/ml increased the death from 30 to 50% with the corresponding PZQ solution causing only 10% death. The in vivo study reflected of niosome-PZQ over PZQ solution as indicated from significant reduction of adult worm count, hepatic and intestinal egg depositions, hepatic granuloma size, and numbers, with marked reduction of vascular endothelial growth factor expression. The study introduced niosomes as promising carriers for enhanced activity of PZQ.