Abstract
Background/Objectives: Leishmaniasis, caused by protozoa of the genus Leishmania, is a major global health issue due to the limitations of current treatments, which include low efficacy, high costs, and severe side effects. This study aimed to develop a more effective and less toxic therapy by utilizing zein nanoparticles (ZNPs) in combination with a nonpolar fraction (DCMF) from Fridericia platyphylla (Syn. Arrabidaea brachypoda), a plant rich in dimeric flavonoids called brachydins. Methods: Zein nanoparticles were used as carriers to encapsulate DCMF. The system was characterized by measuring particle diameter, polydispersity index, zeta potential, and encapsulation efficiency. Analytical techniques such as FTIR, DSC, and AFM were employed to confirm the encapsulation and stability of DCMF. Antileishmanial activity was assessed against Leishmania amazonensis promastigotes and amastigotes, while cytotoxicity was tested on RAW264.7 macrophages. Results: The ZNP-DCMF system exhibited favorable properties, including a particle diameter of 141 nm, a polydispersity index below 0.2, and a zeta potential of 11.3 mV. DCMF was encapsulated with an efficiency of 94.6% and remained stable for 49 days. In antileishmanial assays, ZNP-DCMF inhibited the viability of promastigotes with an IC50 of 36.33 μg/mL and amastigotes with an IC50 of 0.72 μg/mL, demonstrating higher selectivity (SI = 694.44) compared to DCMF alone (SI = 43.11). ZNP-DCMF was non-cytotoxic to RAW264.7 macrophages, with a CC50 > 500 μg/mL. Conclusions: Combining F. platyphylla DCMF with zein nanoparticles as a carrier presents a promising approach for leishmaniasis treatment, offering improved efficacy, reduced toxicity, and protection of bioactive compounds from degradation.