Biophysical investigation of promethazine hydrochloride binding with micelles of biocompatible gemini surfactants: Combination of spectroscopic and electrochemical analysis

Abstract

Knowledge of binding parameters for drug and surfactant complexations is crucially vital in order to design effective drug carrier systems with requisite features. To this end, this work was designed to demonstrate the biophysical characterization of the interaction of a phenothiazine drug promethazine hydrochloride (PMT) with relatively lower cytotoxic and easily degradable biomimetic micellar self-assemblies of oxy-diester functionalized gemini surfactants (C_m-E2O-C_m, m = 12, 14 and 16), possessing different hydrophobic character. The binding propensity of C_m-E2O-C_m increases upon increasing the hydrophobic tail length as manifested through both intrinsic fluorescence and absorption spectral profiles of PMT ̶ C_m-E2O-C_m, showing 1:1 stoichiometry. K_sv values also follow the trend of increasing hydrophobic character (i.e., C₁₂-E2O-C₁₂ < C₁₄-E2O-C₁₄ < C₁₆-E2O-C₁₆). Moreover, the determined thermodynamic parameters, particularly the positive values of ΔH_b^o and ΔS_b^o, reveal that the involved complexations are dominated by the hydrophobic interactions. In addition, micropolarity assay was done to deduce the microenvironmental changes upon PMT ̶ C_m-E2O-C_m complexations. Beside this, comparative appraisal of all the three systems helps to underpin a reasonable knowledge of the effect of structural variation of surfactants on their binding ability with drug which, in turn, may also open new avenues for the designing of potential tunable drug carrier systems.

Keywords: C(m)-E2O-C(m) gemini surfactants; Hydrophobic interactions; PMT.