Physicochemical characterization of polyoxyethylene (POE)-based nonionic surfactants in single and mixed micellar...

This work reports the nanoscale micellar formation in single and mixed surfactant systems by combining an amphiphilic graft copolymer, Soluplus® (primary surfactant), blended with other polyoxyethylene (POE)-based nonionic surfactants such as Kolliphor® HS15, Kolliphor® EL, Tween-80, TPGS®, and Pluronics® P123 in an aqueous solution environment. The solution behaviour of these surfactants as a single system were analyzed in a wide range of surfactant concentrations and temperatures. Rheological measurements revealed distinct solution behaviour in the case of Soluplus®, ranging from low-viscosity (η) and fluid-like behavior at ≤20% w/v to a highly viscous state at ≥90% w/v, where the loss modulus (G'') exceeded the storage modulus (G'). Interestingly, P123 exhibited thermoreversible gelation at 50% w/v, with G' > G'' at 25 °C reversing to G'' > G' at 50 °C. Other POE-based surfactants retained Newtonian flow behaviour under all tested conditions. Dynamic light scattering (DLS) and small-angle neutron scattering (SANS) studies depicted large spherical micelles (R_c ≈ 13.0 nm at 25 °C) for 5% w/v Soluplus® compared to other POE-based nonionic surfactants, while 5% w/v P123 underwent a morphological transition from spherical to ellipsoidal micelles upon temperature variation. In mixed micellar systems, maintaining a total concentration of 5% w/v displayed synergistic interactions, particularly in Soluplus® : P123 and Soluplus® : Tw-80 combinations, where the cloud point (CP) increased significantly (∼29 °C to ∼80-86 °C). In mixed micellar systems, DLS analysis revealed a transition from bimodal to unimodal distributions with increasing Soluplus® content, indicating micelle integration and restructuring. SANS analysis confirmed an ellipsoidal transition in the Soluplus® : P123 system due to strong hydrophobic-hydrophilic interactions. Moreover, these nanoscale entities were assessed for the solubilization enhancement of a hydrophobic anticancer drug, Quercetin (QCT), using UV-visible (UV-vis) spectroscopy in both single and mixed systems. Soluplus® alone exhibited the highest solubilization (∼31.8 μg mL^-1; ∼79.6-fold) while low to moderate proportions of Soluplus® (≤0.5 weight fraction) led to enhanced QCT solubility due to synergistic effects, with notable improvements observed in Soluplus® : P123 (∼17.1 μg mL^-1; ∼42.8-fold) and Soluplus® : HS15 (∼19.4 μg mL^-1; ∼48.5-fold) systems. The in vitro drug release profiles were fitted using various kinetic models, with the Higuchi model providing the best fit (R² = 0.9460-0.9874), indicating a diffusion-controlled mechanism in both single and mixed systems.