Preparation of inhalable quercetin-β-cyclodextrin inclusion complexes using the supercritical antisolvent process for the prevention of smoke inhalation-induced acute lung injury

Abstract

Quercetin (Que) is a natural flavonoid with good anti-inflammatory and anti-apoptosis activities, but its poor water solubility and low bioavailability restrict its clinical application. Cyclodextrin inclusion is one effective method to improve the solubility of Que. In this study, Que-β-cyclodextrin inclusion complexes (Que-β-CD) were prepared using the supercritical antisolvent (SAS) process with supercritical carbon dioxide (SCCO2) and the grinding method, called S-Que-β-CD and G-Que-β-CD, respectively. Que-β-CD was identified with Fourier transform infrared spectroscopy and the X-ray diffraction method. S-Que-β-CD powders had a higher loading efficiency (19.81%) and drug release (71.76%), the smaller mass median aerodynamic diameter (2.83 µm), and the larger fine particle fraction (48.74%) than G-Que-β-CD powders, indicating the SAS process suitable for the preparation of Que-β-CD and S-Que-β-CD suitable for pulmonary inhalation. Pulmonary delivery of S-Que-β-CD showed good protection of the mouse lung from smoke inhalation-induced acute lung injury (SI-ALI), which was indicated by reduced pulmonary edema, high percutaneous oxygen saturation, weak inflammation and apoptosis, and the recovery of body weight. The SAS process is the optimal preparation method to obtain inhalable S-Que-β-CD powders with accelerated drug release, high lung deposition and enhanced therapeutic efficiency.