Electrospun Gelatin Nanofibers Encapsulating Cyclodextrin–Eugenol and Cyclodextrin–Thymol Inclusion Complexes for Nutraceutical Delivery

Bioactive compounds such as eugenol and thymol offer significant health benefits but suffer from poor aqueous solubility and stability. To address these limitations, inclusion complexes (ICs) of eugenol and thymol with hydroxypropyl-β-cyclodextrin (HP-β-CD) were prepared and subsequently encapsulated into fast-disintegrating gelatin nanofibers via electrospinning using an acetic acid/water solvent system. For comparative purposes, IC-loaded and CD-free gelatin films were also fabricated to evaluate structural and functional differences. Scanning electron microscopy (SEM) confirmed the production of uniform, bead-free submicron fibers. Structural analyses via Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC) verified successful complexation and homogeneous incorporation, while thermogravimetric analysis (TGA) demonstrated the enhanced thermal stability of the bioactive agents. ¹H NMR analysis determined the complexation stoichiometry as ∼0.5:1 for eugenol and ∼0.7:1 for thymol systems. In terms of functional performance, nanofibrous mats demonstrated superior water solubility compared to films, with IC-loaded nanofibers reaching up to 87.7% solubility versus 56.4% for film formulations. Furthermore, high-performance liquid chromatography (HPLC) analysis revealed that IC-loaded nanofibers offered significantly faster and higher release rates. While films exhibited a slower profile, nanofibers achieved burst release within 10 min, and the inclusion of CDs enhanced the release capacity by 2- to 3-fold compared to pure bioactive-loaded fibers. These quantitative comparisons confirm that electrospun gelatin nanofibers containing HP-β-CD ICs provide a robust platform for the rapid oral delivery of natural bioactives.