Hypothesis/background: Tetronic (R) is a family of four-armed amphiphilic block copolymers of polyethylene oxide (PEO) and polypropylene oxide (PPO) that self-aggregate to form micelles and hydrogels. Due to their temperature and pH-responsiveness, they are emerging as smart nanomaterials in the area of drug delivery. Here we propose the use of Tetronic 1307 (T1307) as a nanocarrier of miltefosine (MF), a zwit-terionic alkylphospholipid highly active against leishmaniasis, one of the most threating neglected trop-ical diseases. Given the amphiphilic nature of the drug, both surfactants can combine to form mixed micelles, reducing the cytotoxicity of MF by lowering its dose and improving its internalization, hence its antileishmanial effect.Experiments: The structure of the T1307 micelles, MF micelles, mixed micelles and hydrogels, formed in buffered solution (pH = 7.4) at different concentrations has been investigated in-depth by a combination of small-angle neutron scattering (SANS), dynamic light scattering (DLS), fluorescence spectroscopy and nuclear magnetic resonance methods (1D, 2D NOESY, and diffusion NMR). The cytotoxicity of the aggre-gates in macrophages has been assessed, as well as the antileishmanial activity in both Leishmania major promastigotes and amastigotes.Findings: T1307 and MF combine into mixed aggregates over a wide range of temperatures and com-positions, forming ellipsoidal core-shell mixed micelles. The shell is highly hydrated and comprises most of the PEO blocks, while the hydrophobic core contains the PO blocks and the MF along with a fraction of EO and water molecules, depending on the molar ratio in the mixture. The combination with T1307 amplified the leishmanicidal activity of the drug against both forms of the parasite and dramatically reduced drug cytotoxicity. T1307 micelles also showed a considerable leishmanicidal activity without exhibiting macrophage toxicity. These results support the use of T1307 as a MF carrier for the treatment of human and animal leishmaniasis, in its different clinical forms.