This study aimed to create a new nanotherapeutic strategy by combining an interleukin-10 (IL-10) peptide antagonist with amphotericin B (AmB) to boost antileishmanial effectiveness and reduce toxicity. The IL-10 peptide antagonist, identified through in-silico analysis and exhibiting minimal cytotoxicity (95% promastigote viability at 20 µg/mL), was synthesized and linked to AmB using chemical cross-linkers. This conjugate was then encapsulated within gamma-cyclodextrin to form uniform nanoparticles (~40 nm). The particles were characterized using Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM). Both in vitro and in vivo experiments assessed parasite load, immune response, and safety. The nanoformulation markedly decreased parasite burden and enhanced amastigote clearance, confirmed by real-time PCR. Cytokine analysis showed increased levels of IL-12 and other protective cytokines, indicating improved immune modulation. Hematological, biochemical, and splenomegaly assessments demonstrated better safety and therapeutic outcomes compared to AmB alone. The IL-10 antagonist–AmB nanoformulation offers a promising immunomodulatory treatment for leishmaniasis, with enhanced efficacy and safety suitable for application, especially in immunocompromised patients.
Kumar, A., Tiwari, R., Kumari, S., Ranjan, R., Kumar, V., Vedika, S., … Das, P. (2025). Cyclodextrin-AmB-IL-10 antagonist peptide nanoparticles treat leishmaniasis more effectively than conventional AmB. Nanomedicine, 1–15. https://doi.org/10.1080/17435889.2025.2552099