Baicalin is a natural active ingredient known for its medicinal properties and a broad spectrum of pharmacological activities, including antimicrobial, antioxidant, antiviral, and anticancer effects. However, its application is hindered by its poor water-solubility. In this study, we aimed to enhance the water solubility of baicalin by embedding it within the hydrophobic cavity of hydroxypropyl-β-cyclodextrin through supramolecular assembly to form inclusion complexes. The inclusion complexes were subsequently processed into nanofiber membranes suitable for application on skin and wounds using coaxial electrostatic spinning. The inclusion complexes and nanofiber membranes were analyzed and characterized using high-performance liquid chromatography (HPLC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The combined results from XRD, FT-IR, and TGA confirmed that baicalin successfully formed inclusion complexes with cyclodextrin, resulting in an increase in water solubility from 0.0170 mg/mL to 8.9600 mg/mL, representing a 527-fold enhancement. Additionally, the inclusion complexes demonstrated superior antimicrobial activity against E. coli, S. aureus and C. albicans, as well as higher free radical scavenging rates compared to native baicalin. After the inclusion complexes were transformed into nanofiber membranes via coaxial electrospinning, their properties remained unchanged, and they continued to exhibit excellent antimicrobial and antioxidant activities. In the in vitro release assay, nearly 90% of the drug (baicalin) was released from the nanofiber membranes over a period of time, indicating sustained release. Furthermore, the molecular docking mechanism of baicalin and cyclodextrin was elucidated through molecular docking simulations, establishing a theoretical foundation for the synthesis of inclusion complexes in the computational studies. This study reports the successful fabrication of water-soluble, antimicrobial nanofiber membranes containing bioavailable baicalin, which have potential clinical applications in the development of wound dressings and drug delivery systems utilizing plant-extracted bioactive compounds.
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