Liposomal and Micellar-Based Nanoformulations of Fluorinated Curcumin Derivative and Naringenin—Comparative Studies

Background/Objectives: Poor aqueous solubility and low bioavailability limit the therapeutic use of many hydrophobic anticancer agents. This study developed liposomal and polymeric micellar formulations of a fluorinated curcumin derivative (FCur) and naringenin (NG), prepared as single-compound and mixed systems, and compared their physicochemical and biological properties. Methods: Soluplus®-based polymeric micelles and POPC:DOTAP liposomes were prepared by the thin-film hydration method and characterised using dynamic light scattering (DLS), zeta potential measurements, HPLC, NMR relaxation studies, and in vitro cytotoxicity assays. Results: Polymeric micelles formed homogeneous dispersions with particle sizes below 95 nm and a slightly negative zeta potential (~−3 mV), whereas liposomes were larger (>130 nm) and strongly positively charged (>+40 mV). Both systems achieved high encapsulation efficiencies (>72% for FCur and >95% for NG). NMR relaxation studies revealed more restricted molecular dynamics within liposomal bilayers and greater motional freedom in micelles. In biological studies, FCur and mixed liposomes exhibited the highest overall cytotoxicity against bladder (5637), prostate (LNCaP) cancer as well as normal fibroblast (MRC-5) cell lines, compared with the free compounds and polymeric micelles. Notably, polymeric micelles with FCur (single and mixed) exhibited a more favourable differential cytotoxicity response between bladder cancer and normal cells. Conclusions: These findings demonstrate that the nanocarrier system plays a critical role in determining both molecular dynamics and biological performance of encapsulated agents.