Pluronic F127/Pluronic P123/vitamin E TPGS mixed micelles for oral delivery of mangiferin and quercetin: Mixture-design optimization, micellization, and solubilization behavior

Mixed micelles (MMs) of Pluronic F127 (F127), Pluronic P123 (P123), and Vitamin E TPGS (TPGS) copolymers were prepared by the thin-film sonication method to encapsulate two phenolics with different polarities: magniferin (MGF) and quercetin (QCT). Mixture design was applied for the multi-response optimization of formulations of MGF-loaded MMs (MGF-MMs) and QCT-Ioaded MMs (QCT-MMs) with high encapsulation efficiency (EE) and drug loading (DL), but low critical micelle concentration (CMC). The optimal mass fractions of F127/P123/TPGS were 0.120/0.328/0.552 for MFG-MMs and 0.131/0.869/0.000 for QCT-MMs, providing EE (>95% (w/w)) and DL (>4.5% (w/w)) higher than those obtained by their individual copolymer components. The CMCs of MFG/QCT-MMs, detected by dynamic light scattering (DLS). were 0.009 +/- 0.001 and 0.011 +/- 0.001% (w/v), respectively, slightly lower than those obtained by profile analysis tensiometry (PAT). The results revealed that the PAT-CMC represented complete MM formation, while the DLS-CMC detected mono-molecular micelles. The MGF/QCT-MMs showed spherical morphology with diameters of 14.26 +/- 0.52 and 21.50 +/- 0.37 nm, and their zeta-potentials were -2.89 +/- 1.70 and -3.22 +/- 1.92 mV, respectively. Nuclear overhauser effect spectroscopy showed that MGF located in both hydrophilic and hydrophobic parts of MMs by orienting its xanthone backbone towards the core, but its glucoside close to the corona. QCT was preferentially located in the PPO core. Both MGF/QCT-MMs had excellent dissolution ability and sustained release in the simulated gastrointestinal environment. This study demonstrated that mixture design was successfully applied for multi response optimization MM formulations of MGF and QCT, and the developed MMs had potential application as nanoparticle-based drug delivery systems. (C) 2018 Elsevier B.V. All rights reserved.