Therapeutic Potential of 3D-Printed Nifurtimox for Chagas Disease: Effects on Survival, Parasitemia Control and Immune Modulation.

Abstract

OBJECTIVE: The Trypanosoma cruzi immunopathology is sustained by a progressive inflammatory process triggered by parasite antigens, resulting in structural and functional changes in infected organs. Current etiological treatments of benznidazole and nifurtimox show limited efficacy and high toxicity, particularly during chronic infection stages. To address these limitations, a novel 3D printing formulation was applied to nifurtimox (3D nifurtimox) to improve its dissolution and reduce cytotoxicity. This study evaluated the therapeutic efficacy of 3D nifurtimox in experimental T. cruzi infection. METHODS: Female Swiss mice were infected with 4 × 10trypomastigotes of T. cruzi (Y strain) and treated orally for 28 days with nifurtimox (conventional or 3D) at doses of 25, 50 or 100 mg/kg or benznidazole 100 mg/kg. Survival rates, parasitemia and inflammatory profiles in cardiac and skeletal muscles were assessed through quantification of cytokines TNF, IL-6, CCL2 and IL-10. RESULTS: 3D nifurtimox at 50 and 100 mg/kg showed more efficacy in controlling blood parasites in mice surviving and regulating inflammatory cytokine patterns in cardiac and skeletal muscle tissues than conventional nifurtimox. In addition, 3D nifurtimox 100 mg/kg demonstrated complete parasite clearance and sustained protection even under immunosuppression. The improved efficacy is likely related to enhanced dissolution and bioavailability afforded by the 3D printing process, which transformed nifurtimox into an amorphous solid state. CONCLUSION: 3D nifurtimox represents a promising new version of nifurtimox capable of being used in low doses with comparable or superior effects to benznidazole (100 mg/kg) and can be considered a promising tool for anti- T. cruzi therapies.