Synergistic Micellization and Vesicle Formation in Bile Salts and Dihexadecyldimethylammonium Bromide Mixed Systems

The design of tunable self-assembly systems is increasingly important for the development of advanced nanostructures in biomedical applications. Single-surfactant assemblies often suffer from limited stability and adaptability, whereas mixed surfactant systems, particularly those combining biologically relevant bile salts with double-tailed cationic surfactants, offer enhanced physicochemical properties. However, comprehensive experimental investigations into their micellar interactions, thermodynamic stability, and aggregation morphologies remain limited. In this study, the self-assembly behavior of sodium cholate (NaC) and sodium deoxycholate (NaDC) with dihexadecyldimethylammonium bromide (DHDAB) in aqueous solution was systematically examined. Surface tension and conductivity measurements across varying mole fractions were analyzed using the Clint, Rubingh, and Rosen models to determine the critical micelle concentration (CMC), surface excess concentration (Γ_max), minimum molecular area (A_min), and interaction parameters (β_m, β_o), along with the thermodynamic characteristics of micellization. Negative interaction parameter values and consistently low CMCs across all compositions confirmed strong synergistic interactions between the amphiphilic constituents. The thermodynamic stability of micellization is governed by electrostatic complementarity, hydrophobic chain disparity, intermolecular hydrocarbon interactions, and ion–dipole forces. Complementary structural analyses using dynamic light scattering (DLS), small-angle neutron scattering (SANS), and transmission electron microscopy (TEM) revealed the formation of vesicular micelles, consistent with predictions of the packing parameter and cooperative self-assembly. Thermodynamic analyses further confirmed that micellization is spontaneous and predominantly driven by entropy. Overall, these findings demonstrate that bile salt–cationic surfactant mixtures can generate stable and tunable vesicular assemblies, providing a molecular framework for nanocarrier development, controlled drug release, and sustainable material formulations, while emphasizing the need for further studies on their biocompatibility and functionalization for targeted delivery.