Thymoquinone-Micellar Interactions: A physico-chemical investigation at molecular level

•Study explores TQ-micellar interaction under surfactant and temperature variations.•Examines volumetric and acoustic parameters of TQ with surfactants.•TQ's hydrophobic nature influences intermolecular forces.•UV spectroscopy reveals strong TQ-TX-100 binding, pertinent to drug delivery. Thymoquinone (TQ) is considered the most-active component of the well-known essential oil of the black cumin/seeds (Nigella sativa L.), also known for its wide-spectrum anticancer and other pharmacological potentials since ancient times. Apart from its thermo- and photo-sensitive nature, TQ has also been reported to demonstrate strong hydrophobicity and low bioavailability. These physico-chemicals, properties hinder the development of a successful oral dosage formulation. Interaction of the pharmacologically active molecule with biological membranes is crucial step to manifest health-related effects. However, further insight into the biophysical interactions of “active” natural chemotherapeutics with cellular membranes can play a vital role in designing and developing new anti-cancer regimens. In this context pseudo-membrane models comprising ionic and non-ionic micelles offer a useful way to explore in vitro drug-membrane interactions at the molecular level. The present study focuses on the physicochemical interactions of a thymoquinone (TQ) with micelles of ionic (dodecyl trimethylammonium bromide, DTAB; and sodium dodecyl sulfate, SDS) and non-ionic (tween-80 and TX-100) surfactants at the molecular level in aqueous medium. Volumetric and acoustic parameters (apparent molar volume (ɸV), isentropic compressibility (Ks), apparent molar isentropic compressibility (ɸk), specific acoustic impedance (Z), relative association (RA), intermolecular free length (Lf)) are calculated from experimental data of density and sound velocity and interpreted in terms of solute/solvent–solute/solvent interactions using the co-sphere overlap model and the electrostriction effect. Further, UV spectroscopy and conductivity studies are used to predict the locus of TQ in the micelles, binding constant (Kb), partition coefficient (Kc), and free energy changes of TQ-micelle systems in the presence of surfactants. The results show that the binding and partitioning of TQ is more significant with TX-100 as compared with other ionic and non-ionic surfactants used.