Efficacy of benznidazole-loaded nanoparticles on an animal model of acute Chagas disease

MURACA, GIULIANA; PIÑERO, MARÍA BELÉN; MARCHETTO, MATIAS ILDEBRANDO; ALBA SOTO, CATALINA D.; CHAIN, CECILIA YAMIL; CISNEROS, JOSÉ SEBASTIÁN; ISLAN, GERMÁN A; TALEVI, ALAN

Congreso; XVII Congreso de la Sociedad Latinoamericana de Parasitología; 2024

Federación Latinoamericana de Parasitología

Chagas disease is a Latin American endemic parasitic disease, that affects nearly 6-7 million people worldwide. The first-line pharmacotherapy is benznidazole (BNZ), which has shown significant adverse effects that often compromise patient’s adherence to the pharmacological treatment. In order to optimize the drug distribution and overall bioavailability of BNZ, we encapsulated it in pharmaceutical nanocarriers (lipid and polymeric formulations). Our previous findings showed no significant differences between the formulations and the free drug in terms of in vitro efficacy against trypomastigotes and amastigotes and revealed that an ingredient of the lipid formulation (myristyl myristate, MM) was toxic to the parasites. When tested on mammalian cells, both formulations exhibited diminished cytotoxicity compared to the free drug, which could potentially reduce the occurrence of adverse effects. Here, our goal was to evaluate the in vivo efficacy of our BNZ formulations in an animal model of acute Chagas disease. For this, nanoparticles were obtained using the emulsification method by ultrasonication. Lipidic nanostructured carriers were obtained with MM as the solid lipid, the core-disorganizing liquid lipid GTCC-LQ, and poloxamer P188 as the surfactant. The same surfactant and the neutral polymer Eudragit® NE30D were used to prepare the polymeric nanoparticles. Size, polydispersity index, and Zpotential were measured as quality control criteria. Mice were provided by the Institute of Microbiology and Medical Parasitology (IMPaM, UBA). Free and encapsulated BNZ (10 mg/kg/d) was administered orally during a 5-day treatment to Balb/c female mice, 3-4 weeks old (n=5 per group), infected with 1,000 RA trypomastigotes intraperitoneally. As control groups, the drug vehicle (20% DMSO) and the empty nanoparticles (equivalent to the concentration of nanoparticles that would encapsulate 10 mg/kg of BNZ) were included. Follow-up consisted of measuring parasitemia every two days. Our results showed an increase in the survival percentage of mice treated with the encapsulated BNZ compared to vehicles, and a reduced survival in comparison with free BNZ. We also found that mice treated with the control of lipidic empty nanoparticles had a longer survival rate in comparison to mice treated with empty polymeric nanoparticles and the free BNZ vehicle, which seems consistent with our previous findings on the anti-parasitic effect of MM. At the end of the experiment, mice were euthanized using CO2. All procedures were performed according to the protocol approved by the Ethics Committee for Animal Experimentation (CICUAL) of the University of Buenos Aires, Argentina (Fmed, UBA) (Res. Nº 4081/04).