Comparative Thermodynamic Analysis of Micellar Solubilization and Cyclodextrin Inclusion of Serotonin (5-HT) in Aqueous Media

This study presents a comparative thermodynamic analysis of serotonin (5-hydroxytryptamine, 5-HT) solubilization in organized aqueous media, namely micellar systems (SDS, CTAC, CTAOH, Brij 700) and cyclodextrin inclusion complexes (β-CD, HP-β-CD, HP-γ-CD). Binding and apparent partition constants were determined by fluorescence titration and analyzed over 298–318 K using Van’t Hoff plots to obtain ΔG°, ΔH°, and ΔS°. Ionic micelles (SDS and CTAC) strongly stabilize 5-HT (ΔG° ≈ −27 to − 32 kJ·mol⁻¹) through predominantly enthalpy-driven processes combining electrostatic and hydrophobic interactions. In contrast, the nonionic micelle Brij 700 exhibits weaker, mainly entropy-driven stabilization (ΔG° ≈ −20 kJ·mol⁻¹), reflecting hydrophobic transfer and desolvation effects. Cyclodextrins form discrete 1:1 host–guest complexes with moderate affinity, with HP-β-CD showing the highest stability (ΔG° ≈ −26 kJ·mol⁻¹), consistent with favorable cavity–guest complementarity. These results reveal fundamental thermodynamic differences between cooperative micellar pseudophase partitioning and classical cyclodextrin inclusion, providing mechanistic insight for rational carrier selection in amphiphilic drug and neurotransmitter delivery systems.