Physicochemical characterization of polyoxyethylene (POE)-based nonionic surfactants in single and mixed micellar environments for anticancer drug solubilization enhancement

Abstract

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.