Retinoic acid-loaded nanoparticles enhance macrophage-mediated control of

Background/aim: Visceral leishmaniasis, primarily caused by Materials and methods: ATRA-loaded SLNs were prepared and characterized for size, polydispersity index, zeta potential, and morphology. Their antileishmanial activity was evaluated against extracellular Results: Neither free ATRA nor ATRA-loaded SLNs exhibited significant inhibitory activity against extracellular promastigotes at concentrations up to 75 μM. In contrast, both forms of ATRA demonstrated marked dose-dependent inhibition in infected macrophages, with a significantly enhanced intracellular response observed in the SLN formulation, while maintaining excellent biocompatibility in noninfected macrophages. Enhanced uptake and sustained intracellular release are likely contributors to the improved efficacy of the SLN system. Conclusion: The findings reveal that ATRA exerts its antileishmanial activity primarily through host-dependent mechanisms that become apparent within infected macrophages, and that encapsulation into SLNs markedly amplifies this intracellular effect while preserving cell viability. ATRA-loaded SLNs thus represent a promising host-directed therapeutic strategy for the treatment of visceral leishmaniasis.