Abstract: The micelles of zwitterionic betaine surfactant, SB3-12, have good biocompatibility and smaller negative charge density on the surface due to the electrostatic neutralization on the polar head that consists of two opposite charges. However, the available charge density on the micellar surface is essential for its application as a drug carrier owing to either the increased binding to cells or its favorable delivery into some specific organs under physiological conditions. This also facilitates the selective solubilization of drug molecules, depending on the interaction between the surfactant headgroup and drug molecule. When an anionic sodium dodecyl sulfate (SDS) is incorporated into SB3-12 micelles, the negative charge density of the micellar surface (from the sulfonic groups) can be continuously adjusted with a negative-positive order of the zwitterionic headgroup, where the electrostatic interaction occurs with the positively charged quaternary ammonium in the inner layer of the micellar polar region. Accordingly, positive micelles with adjustable charge density could be obtained if a cationic surfactant is incorporated into the micelles of the zwitterionic surfactant with a positive-negative headgroup. Using isothermal titration calorimetry, it is determined that a strong synergistic interaction occurs between SB3-12 and SDS, followed by a significant decrease in the mixed critical micelle concentration (CMC) and micellization enthalpy, which is mainly caused by weak electrostatic interaction. The synergistic effect is similar to that in the case of oppositely charged surfactant mixtures; however, the mixtures of zwitterionic and ionic surfactants do not form catanionic precipitates even at an equimolar ratio. When rutin, a model drug, is added to the SB3-12/SDS solution mixture, both SDS and the negatively charged rutin, obtained from the dissociation of the hydrogen of 7-hydroxyl group of rutin, can together interact with SB3-12 forming mixed micelles. The dissolved rutin molecules do not change the mixed CMC and the solubility of rutin is approximately constant when the composition of the mixed surfactants is in the range of 0.5 < x_SB3-12 < 1; however, these can significantly enhance the electrostatic interaction between the mixed micelle and rutin molecule as x_SB3-12 decreases. This can possibly allow the controlled release of rutin. UV-visible absorption spectroscopy and ¹H NMR spectroscopy reveal that in SB3-12 micelles, the A ring of rutin is located near the positively charged quaternary ammonium group of SB3-12, and the B ring is located between the oppositely charged headgroups of SB3-12. In SDS micelles, the B ring is located on the palisade layer and the A ring and disaccharide are exposed to the aqueous phase. For the mixed SB3-12/SDS micelles, as the molar fraction of SDS increases, the electrostatic attraction toward the A ring weakens. The role of ionic surfactant in adjusting the surface charge density of the zwitterionic surfactant micelles allows the fine-tuning of the physical and chemical properties of polar micellar region, thereby exhibiting the potential for selective solubilization and controlled release of drugs.

Key words: Zwitterionic surfactant, Mixed micelle, Micellar surface charge, Rutin, ITC, Interaction