Partitioning‐Dominated Encapsulation of DL‐DOPA in Sodium Deoxycholate Micelles: Thermodynamic Insights Into Micellization and Binding

The therapeutic performance of DL‐DOPA (DOPA), the primary precursor used in the management of Parkinson’s disease, is limited by its complex aqueous behavior and moderate solubility. This study presents a comprehensive thermodynamic investigation of DOPA encapsulation in sodium deoxycholate (SDC) micelles, aiming to elucidate the relative contributions of micellization, binding, and partitioning mechanisms. Surface tension, conductometry, and UV–visible spectroscopy were systematically employed to characterize the drug–surfactant interactions. The presence of DOPA induced a significant 27‐fold reduction in the critical micelle concentration (CMC) of SDC, decreasing from 4.93 × 10 −3 M to 1.84 × 10 −4 M, indicating strong cooperative interactions. Surface thermodynamic parameters confirmed the spontaneous nature of both interfacial adsorption and micelle formation. Quantitative analysis revealed that drug encapsulation is predominantly governed by micellar partitioning rather than simple binding, as evidenced by a high partition coefficient ( K x = 1.703 × 10 6 L/mol) and a strongly negative standard transfer free energy (Δ G x = −35.566 kJ/mol). Spectroscopic analysis further confirmed complex formation with a binding constant ( K b = 6.05 × 10 4 L/mol). The combined thermodynamic and spectroscopic evidence demonstrates that DOPA solubilization in SDC micelles is primarily driven by energetically favorable partitioning, supported by cooperative electrostatic and hydrogen‐bonding interactions. These findings provide a quantitative physicochemical basis for the rational design of bile salt–based nanocarrier systems for zwitterionic pharmacological entities.