Background: Baicalein (BA) is a poorly soluble flavonoid with limited oral bioavailability. This study aimed to enhance the solubility and nasal absorption of the compound using a dual-carrier system that combines cyclodextrin inclusion complexes and thermosensitive hydrogels. Methods: The inclusion complexes of BA with hydroxypropyl-β-cyclodextrin (HP-β-CD) or sulfobutyl-β-cyclodextrin (SBE-β-CD), namely BA-HP-β-CD and BA-SBE-β-CD, were prepared via solution stirring and characterized by solubility, dissolution, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis-differential scanning calorimetry (TG-DSC), and Madin-Darby canine kidney (MDCK) cell permeation. The optimal complexes were incorporated into chitosan/β-glycerophosphate thermosensitive hydrogels (BA/HP-Gel and BA/SBE-Gel), followed by evaluations of gelation properties, in vitro release, and in vivo pharmacokinetics in rats. Results: The water solubility of BA-HP-β-CD and BA-SBE-β-CD increased 572 and 582 times, with MDCK permeability enhanced by 5.3 and 2.9 times, respectively. Both hydrogels showed rapid solution-gel transition at nasal temperature and sustained release. Following intranasal administration, BA/HP-Gel and BA/SBE-Gel achieved relative bioavailabilities of 623.5% and 697.8%, respectively, compared with BA-Gel. Conclusions: The dual-carrier platform effectively improved BA solubility, permeability, and nasal bioavailability, offering a promising strategy for nasal delivery of poorly soluble drugs.

Purpose: To address the challenges of low water solubility and poor bioavailability of quercetin (QUE), which limit its clinical application, and to develop an optimized oral solid dispersion formulation to enhance its absorption. Methods: Quercetin solid dispersions (QUE-SD) were prepared using the solvent evaporation method. The study involved screening single-factor and combined carriers, followed by formulation optimization via orthogonal analysis based on solubility and cumulative dissolution rates. The optimized dispersions were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). Additionally, transmembrane transport was evaluated using Caco-2 and MDCK cell models, and oral bioavailability was assessed through pharmacokinetic studies in rats. Results: The optimal formulation was determined to be a 1:3:1 ratio of Quercetin, Hypromellose E5, and polyvinylpyrrolidone K13-18, with an evaporation temperature of 55 °C and a mixing time of 4 h. In cell transport models, the apparent permeability coefficient of QUE-SD increased by 1.14 (Caco-2) and 1.1 (MDCK) times. Pharmacokinetic data confirmed that the solid dispersion significantly improved both the absorption rate and oral bioavailability of quercetin in rats. Conclusions: The prepared quercetin solid dispersion effectively enhances the water solubility, transmembrane transport, and systemic absorption of quercetin. These findings provide a viable strategy and theoretical basis for developing high-bioavailability oral formulations of quercetin.