​Curcumin (CUR) is a bioactive natural compound with potent antioxidant and anticancer properties. However, its poor water solubility has been a major limitation against its widespread clinical use. The aim of this study was to develop a nanoscale formulation for CUR to improve its solubility and potentially enhance its bioactivity, by leveraging the self-assembly behavior of tannic acid (TA) and amphiphilic poloxamers to form CUR-entrapped nanoassemblies. To optimize drug loading, formulation variables included the CUR: TA ratio and the type of amphiphilic polymer (Pluronic® F-127 or Pluronic® P-123). The optimal CUR nanoparticles (NPs) were around 200 nm in size with a high degree of monodispersity and 56% entrapment efficiency. Infrared spectroscopy confirmed the presence of intermolecular interactions between CUR and the NP formulation components. X-ray diffraction revealed that CUR was ​