Ionic lipid–surfactant complex based on phosphatidylcholine and sodium dodecyl sulfate for enhanced curcumin encapsulation and sustained delivery

Developing stable, efficient nanocarriers for hydrophobic anticancer agents remains a major challenge in pharmaceutical nanotechnology. In this study, we engineered a novel ion-pair amphiphile through electrostatic complexation between zwitterionic phosphatidylcholine and the anionic surfactant sodium dodecyl sulfate (SDS), forming a phosphatidylcholine–SDS (P-SDS) ionic complex with enhanced hydrophobicity and self-assembly capability. The resulting hybrid amphiphile was further stabilized with Tween-80 and formulated into nanoscale micellar structures to encapsulate curcumin. 1H-NMR and FT-IR spectroscopy confirmed the formation of the P-SDS ionic complex, while DSC analysis showed the disappearance of crystalline curcumin, indicating successful amorphous dispersion within the micellar core. Fluorescence spectroscopy revealed a low critical micelle concentration (CMC) of 3.1 × 10−4 M, suggesting favorable thermodynamic stability of the self-assembled system. Dynamic light scattering measurements showed an average particle size of approximately 239 nM with a strongly negative zeta potential ranging from −37 to −44 mV, indicating good colloidal stability. The optimized formulation achieved 19% drug loading with an encapsulation efficiency of 39.8%. In vitro release studies showed a biphasic release profile: an initial moderate burst followed by sustained curcumin release over 72 h. Morphological analyses using ESEM and TEM confirmed the formation of spherical nanoscale assemblies with relatively uniform morphology. The developed P-SDS nanoassembly is a simple, scalable, and biocompatible platform for delivering hydrophobic therapeutic agents. The ion-pair engineering strategy proposed in this work provides a versatile approach to tuning amphiphilicity, self-assembly behavior, and drug-loading capacity in lipid-based nanocarriers, with potential applicability for passive tumor targeting through the enhanced permeability and retention (EPR) effect.