Preparation, optimization, characterization and in vitro release of baicalein-solubilizing glycyrrhizic acid nano-micelles.

Abstract Glycyrrhizic acid is an amphiphilic molecule, which can form host-guest complexes by self-assembly, thereby encapsulating the guest molecule and increasing its solubility. The complexes can also achieve a controlled release effect for encapsulated drugs, so they have potential as drug delivery-systems. Baicalein is a flavonoid, with many pharmacological activities, but its oral bioavailability is limited by its poor solubility. In this study, glycyrrhizic acid-baicalein nano-micelles were prepared by an ultrasonic-film hydration method. The baicalein-loaded nano-micelles were evaluated by encapsulation efficiency, baicalein loading, particle size, polydispersity index and ζ-potential. A Box-Behnken statistical design was applied to obtain the optimal formulation (glycyrrhizic acid: 90 mg, baicalein: 8 mg, water bath shaking time: 12 h, ultrasonication time: 10 min). Nano-micelles prepared with the optimal formulation improved the solubility of baicalein in water by more than 4,500 times and were characterized by differential scanning calorimetry and Fourier-transform infrared spectroscopy. An in vitro drug release study determined the cumulative drug release of baicalein in pH 6.8 and pH 8.3 buffer medium, after 6 h to be 18.20% and 47.96%, respectively, which indicates that the nano-micelles have a sustained-release effect on baicalein and that the release rate can be modulated by changing the pH.