Composition- and temperature-controlled architecture of pluronic F127–miltefosine mixed micelles

Polymeric micelles have been long used as nanocarriers to improve the solubility and delivery of poorly water-soluble drugs. However, the incorporation of amphiphilic drugs introduces an additional level of complexity, where the drug can contribute directly to the self-assembly process, giving rise to mixed micelles whose structure and properties are determined by the cooperative interactions of both components. Here, we investigate this concept using Pluronic ® F127, a thermoresponsive triblock copolymer, and miltefosine (MF), an amphiphilic drug currently used for the treatment of leishmaniasis. By combining small-angle neutron scattering with complementary light scattering, fluorescence, and NMR methods, we establish a quantitative structural description of F127-MF mixed micelles over a range of polymer-to-drug ratios. MF promotes the formation of mixed micelles by facilitating micellization at lower F127 concentrations and below its critical micellization temperature, while preferentially partitioning into the hydrophobic core. Through manipulation of the polymer-to-drug ratio, the properties of these mixed micelles can be tuned. At high F127 content, the mixed micelles closely resemble those of the pure surfactant, whereas increasing MF fraction induces a transition from polymer-rich to drug-rich aggregates characterized by changes in aggregation number, hydration, and internal organization. Overall, this work establishes an exhaustive characterization of F127–MF mixed micelles as a versatile and tunable colloidal system, providing valuable insights into the design of pharmaceutical formulations based on amphiphilic block copolymers as drug carriers.