Cyclodextrin-AmB-IL-10 antagonist peptide nanoparticles treat leishmaniasis more effectively than conventional AmB

This study aimed to develop a novel nanotherapeutic approach by combining an interleukin-10 (IL-10) peptide antagonist with amphotericin B (AmB) to enhance antileishmanial efficacy while reducing cytotoxicity. A peptide antagonist targeting IL-10, identified via <i>in-silico</i> analysis and showing minimal cytotoxicity (95% promastigote viability at 20 µg/mL), was synthesized and conjugated with AmB using chemical cross-linkers. The conjugate was encapsulated in gamma-cyclodextrin to produce uniform nanoparticles (~40 nm). Characterization was performed using Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM). In vitro and in vivo studies were conducted to assess parasite burden, immune response, and safety parameters. The nanoformulation significantly reduced parasite burden and improved amastigote clearance, as confirmed by real-time PCR. Cytokine profiling revealed elevated IL-12 and other protective cytokines, indicating enhanced immune modulation. Hematological, biochemical, and splenomegaly analyses demonstrated improved safety and therapeutic efficacy compared to AmB alone. The IL-10 antagonist – AmB nanoformulation represents a promising immunomodulatory therapeutic strategy for leishmaniasis. Its enhanced efficacy and safety highlight its potential for application, particularly in immunocompromised patients.