Exploring dye-drug-micelle synergy for enhanced antibiotic delivery and green solubilization: a concentration dependent study on the CTAB/tetracycline/Congo red system using UV–vis spectroscopy and DFT fingerprints

This investigation provides the first report on the micellar encapsulation and binding efficacy of Tetracycline (TC) antibiotic in cetyltrimethylammonium bromide (CTAB) micelles in the presence and absence of Congo red dye (CR) at varied drug concentrations (Drug-Micelle-Dye Synergy) by UV–visible and DFT approaches for Green Solubilization and enhanced Drug Delivery. The critical micelle concentration (CMC*), Gibbs energy of micellization (∆G_m⁰), binding constant (K_b), and Gibbs energy of binding (∆G_b⁰) for (CTAB+TC) and (CTAB+TC + CR) have been evaluated at varied TC concentrations (0.002, 0.0002, and 0.00002 mol L⁻¹). The obtained CMC* value decreases with increasing TC concentrations for both systems, and comparatively, CMC* for (CTAB+TC + CR) is more than that for binary (CTAB+TC) systems. The more negative value of ∆G_m^o has been observed for the binary system as compared to the ternary system. The decrease in negative ∆G_m^o with TC concentrations for both systems suggests enhanced micelle stability and spontaneity, showing TC as an effective micelle promoter. The evaluated K_b has the largest value (369.84 ×10³ for binary and 604.36 ×10³ L mol⁻¹ for ternary systems) at intermediate TC concentration, confirming a stronger and more favorable cooperative binding, and the∆G_b^o also varies accordingly (−20.57, −31.78, and −27.82 kJ mol-1 for binary, and −21.23, −32.99, and −28.38 kJ mol⁻¹ for ternary systems). DFT-optimized structures of TC–CR–CTAB ternary complex show major reorientation relative to each binary. Our DFT calculations also identified this configuration as a very stable ternary complex, with a binding energy of −255.18 kJ mol⁻¹ that is significantly higher than that for binary interactions.