Effect of VAM2-2 and VAM2-2 loaded chitosan nanoparticles in treatment of experimental toxoplasmosis: an experimental study
Background: Toxoplasmosis is a worldwide infection caused by obligate intracellular protozoan parasite, Toxoplasma gondii. The standard treatment of toxoplasmosis is a combination of pyrimethamine, sulfadiazine and antifolates. Many side effects were reported with this combination with no alternative drug therapy or effective vaccine.
Methods: In this study VAM2-2 was designated by TOMOCOMB CARDD approach and a system based on CS NPs was prepared as a potential carrier for VAM2-2 to be evaluated for the first time for their anti-toxoplasma effect in both immunocompetent and immunosuppressed experimental mice. Assessment of drugs effect was achieved through estimating the mortality rate and the survival time of the infected treated mice, studying peritoneal and liver parasite burden, tachyzoites viability and infectivity and ultrastructural tachyzoites changes in comparison with the infected non-treated control animals, were studied. Serum gamma interferon (INFγ) levels were also estimated by enzyme linked immunosorbent assays (ELISA) kits. Drugs safety was biochemically detected by measuring liver enzymes, urea and creatinine in mice sera.
Results: The obtained results showed that VAM2-2, CS NPs and VAM2-2 loaded CS NPs were effective against acute toxoplasmosis. All treating drugs induced a significant increase in the survival time of the infected treated mice. Treated mice showed a statistically significant reduction in the parasite burden, viability and infectivity of tachyzoites harvested from their peritoneal cavities as compared with the infected non-treated controls. EM examination revealed multiple changes in treated tachyzoites. Serum gamma interferon (INFγ) levels were statistically significantly increased in CS NPs and VAM2-2 loaded CS NPs treated mice in comparison to infected untreated mice and those treated with free VAM2-2. Besides, biochemical results showed no evidence of toxicity with all therapeutic agents used. VAM2-2 loaded CS NPs gave the best results in all studied parameters.
Conclusion: all used drugs had promising anti-toxoplasma activities. VAM2-2 loaded CS NPs showed the highest effects in the treatment of acute toxoplasmosis. This will draw the attention to the use of this potential combination as an alternative to the standard therapy in treatment of toxoplasmosis.