Abstract
Toxoplasma gondii is a zoonotic intracellular protozoan with worldwide distribution. Acute and severe toxoplasmosis are commonly reported in patients who suffer from acquired/congenital immune deficiency. This study aimed to synthesize mannosylated paromomycin-loaded solid lipid nanoparticles (PM-SLN-M) and to evaluate them on acute toxoplasmosis. SLN was synthesized and then loaded by 7 mg/mL paromomycin sodium. Mannose coating was performed, and after washing, the size, zeta potential, and loading percentage were calculated. To evaluate the cell toxicity, an MTT assay was performed on Vero cells by different concentrations (log 10−1) of SLN, PM-SLN-M, and PM-SLN. In addition, the anti-Toxoplasma effects were also evaluated using trypan-blue staining and scanning electron microscopy (SEM). An MTT assay was also employed to evaluate the effects of PM and PM-SLN-M on intracellular Toxoplasma. A 6-month stability test of PM-SLN and PM-SLN-M represented that the characteristics all remained constant. The cell viability assay demonstrated that PM-SLN-M had lower cell toxicity (<20%) compared to PM-SLN (<30%) and PM (<40%). Statistical analysis showed that PM-SLN-M significantly killed ~97.555 ± 0.629 (95% CI: 91.901 to 103.209; P < 0.05) of T. gondii tachyzoites. More than 50% of Toxoplasma-infected Vero cells remained viable in concentrations more than 0.07 μg/mL and 7 μg/mL of PM and PM-SLN-M, respectively. SEM analysis showed that T. gondii tachyzoites were changed in both size and morphology facing with PM-SLN-M. Our findings indicated that synthesized PM-SLN-M had anti-Toxoplasma activity without significant host cell toxicity at the highest concentration. Our study demonstrated that PM was able to kill intracellular Toxoplasma in lower concentration in comparison to PM-SLN-M, although PM-SLN-M showed lower cytotoxic effects on Vero cells.
Highlights
Toxoplasma gondii is a zoonotic obligate intracellular protozoan parasite that infects a broad range of warm-blooded animals from birds to humans
Toxicity assay of nanoformulations showed that more than 78.96 ± 0.07% of Vero cells remained viable at the highest concentration (7 mg/mL) of PM-SLN-M (CC50 > 7 mg/mL) while almost 56.85 ± 0.255% of the cells dead using the same concentration of PM (P < 0.05; CC50 > 7 mg/mL)
Comparison of cytotoxicity effects of PM-SLN with PM-SLN-M showed that mannosylation reduced the cell toxicity of the nanodrug from ∼30 to 20% of Vero cells at the highest concentration
Summary
Toxoplasma gondii is a zoonotic obligate intracellular protozoan parasite that infects a broad range of warm-blooded animals from birds to humans. Ingestion of mature oocyst via food and water is the main route of infection (Hill and Dubey, 2016), consumption of raw meat containing cysts, needle injection ( in research laboratory), congenital infection, blood transfusion ( white blood cells), and organ transplantation from an infected person are the other potential routes of transmission (Montoya and Liesenfeld, 2004). Acute infection due to toxoplasmosis ranks high on the list of fatal diseases in HIV/AIDS patients (Hill and Dubey, 2002; Ahmadpour et al, 2019). Taken together with the complications due to acute toxoplasmosis in immunocompromised patients, more recently, the potential role of activated toxoplasmosis in response to the immunomodulatory drugs during inflammatory bowel diseases (IBD) and its pathogenesis was suggested (Mirjalali et al, 2019). Prescription of a standard drug regimen with low side effects is an important issue during acute toxoplasmosis
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