Physicochemical investigation of DL-DOPA interaction with cationic surfactants: Micellization, binding thermodynamics, and solubilization

Abstract

Understanding the interaction between therapeutic agents and surfactant-based drug delivery systems is crucial for designing effective pharmaceutical formulations. This study provides a comprehensive comparative analysis of the physicochemical interactions between the anti-parkinsonian drug DL-DOPA (DOPA) and two cationic surfactants, cetylpyridinium chloride (CPC) and benzalkonium chloride (BKC), in aqueous media. The investigation was conducted using a suite of analytical techniques, including surface tensiometry, conductometry, and UV-Vis spectrophotometry at 25 °C. The results reveal a potent synergistic interaction between DOPA and both surfactants, evidenced by a remarkable depression in the critical micelle concentration (CMC): a 70% reduction was observed for BKC, while a dramatic 98% reduction was recorded for CPC, highlighting the superior efficiency of the latter in forming mixed micelles with DOPA. Thermodynamic analysis revealed that micellization and drug-micelle binding are spontaneous processes (ΔG < 0). DOPA exhibited a significantly stronger interaction with CPC micelles compared to BKC, as evidenced by a higher binding constant (K_b = 12.64 × 10⁴ L/mol for CPC versus 3.14 × 10⁴ L/mol for BKC) and a more favorable partition coefficient (K_x = 27.82 × 10⁴ L/mol for CPC versus 6.7 × 10⁴L/mol for BKC). This enhanced interaction with CPC is attributed to a combination of hydrophobic forces and potential π-π stacking between the pyridinium head group and the aromatic ring of DOPA. The findings demonstrate that both CPC and BKC can effectively interact with and solubilize DOPA, but CPC offers a more favorable binding and partitioning environment. This detailed characterization provides fundamental insights that can guide the rational selection of cationic surfactants for the development of advanced DOPA delivery systems.