In Vitro and In Vivo Trypanocidal Activity of H2bdtc-Loaded Solid Lipid Nanoparticles.

The parasite Trypanosoma cruzi causes Chagas disease, which remains a serious public health concern and continues to victimize thousands of people, primarily in the poorest regions of Latin America. In the search for new therapeutic drugs against T. cruzi, here we have evaluated both the in vitro and the in vivo activity of 5-hydroxy-3-methyl-5-phenyl-pyrazoline-1-(S-benzyl dithiocarbazate) (H2bdtc) as a free compound or encapsulated into solid lipid nanoparticles (SLN); we compared the results with those achieved by using the currently employed drug, benznidazole. H2bdtc encapsulated into solid lipid nanoparticles (a) effectively reduced parasitemia in mice at concentrations 100 times lower than that normally employed for benznidazole (clinically applied at a concentration of 400 µmol kg−1 day−1); (b) diminished inflammation and lesions of the liver and heart; and (c) resulted in 100% survival of mice infected with T. cruzi. Therefore, H2bdtc is a potent trypanocidal agent. Author Summary: The protozoan parasite Trypanosoma cruzi causes Chagas disease, a condition that affects the poorest regions of Latin America mainly. The chronic phase of this disease disables thousands of patients, constituting an important public health issue. The pharmacotherapy that is currently applied to treat the disease emerged many decades ago, is ineffective in most patients, mainly during the chronic phase, and has serious side effects. In a recent study, we showed that the compound 5-hydroxy-3-methyl-5-phenyl-pyrazoline-1-(S-benzyldithiocarbazate) (H2bdtc) is a potential drug candidate against the in vitro trypomastigote form of Tulahuen strains of T. cruzi. Here we report that H2bdtc loaded into solid lipid nanoparticles (H2bdtc-SLNs) displays good trypanocidal activity against the trypomastigote form of the Y strain of T. cruzi both in vitro and in vivo. Our in vivo experiments revealed that H2bdtc-SLN is 100 times more active than benznidazole (BZN), the drug that is commercially available to treat Chagas disease. Surprisingly, this compound has no side effects on the T. cruzi acute phase. Hence, we propose that H2bdtc-SLNs possesses interesting anti-Trypanosoma properties. [ABSTRACT FROM AUTHOR]