Chitosan nanogels for the improvement of benznidazole activity.

Chagas disease, caused by Trypanosoma cruzi, remains a major neglected disease with limited therapeutic options. Benznidazole (Bzn) is the first-line treatment, despite low aqueous solubility, poor bioavailability and significant side effects, which reduce its efficacy, particularly during the chronic phase of infection. Herein, chitosan (CS) nanogels (NGs) obtained by ionic gelation with tripolyphosphate (TPP) and citrate were developed as nanocarriers for Bzn, aiming to improve its antiparasitic performance. CS obtained from renewable crustacean shell waste was purified, characterized, and used to prepare NGs that were applied for Bzn encapsulation. The resulting CS-Bzn-NGs were spherical, positively charged, and stable for at least four weeks, with hydrodynamic diameters ∼250 nm and 77% encapsulation efficiency of the drug. In vitro cumulative release studies showed a Bzn release of 70% within 5 h and complete release after buffer renewal. NGs synthesized with FITC-labeled CS demonstrated efficient uptake by HeLa cells and T. cruzi trypomastigotes without inducing cytotoxicity. The trypanocidal activity of CS-Bzn-NGs was evaluated against trypomastigote and intracellular amastigote forms of three T. cruzi strains belonging to different discrete typing units (Sylvio, RA and Y). CS-Bzn-NGs retained antiparasitic activity comparable to free Bzn and achieved similar efficacy at lower drug concentrations. Therefore, CS-TPP-citrate NGs constitute a promising and sustainable nanomedicine platform for Bzn delivery to enhance chemotherapy for Chagas disease.