Development of electrospun pullulan nanofibers encapsulating naringenin/sulfobutylether-β-cyclodextrin inclusion...

In this study, we have developed a fast-dissolving oral delivery system for naringenin (NN) which is a hydrophobic flavonoid with limited aqueous solubility and stability. The delivery platform is based on the formation of an inclusion complex between NN and sulfobutylether-β-cyclodextrin (SBE-β-CD), followed by incorporation of the complex into electrospun pullulan (PLN) nanofibers (NFs). The NN/SBE-β-CD inclusion complexes (ICs) were prepared in an aqueous system and incorporated into pullulan nanofibers via single-nozzle electrospinning. The developed formulations were thoroughly characterized using a range of analytical techniques, including NMR (1D and 2D-NOESY), FTIR, PXRD, TGA, and SEM. The NMR analysis confirmed the inclusion of NN within the CD cavity through the broader rim, involving interactions between aromatic NN protons and CD's internal protons. The FTIR spectral results indicated molecular interactions among NN, SBE-β-CD and PLN. The SEM demonstrated bead-free, smooth nanofibers (261.03 ± 31.78 nm), while PXRD and TGA confirmed amorphization and thermal stabilization of NN. The nanofibers rapidly disintegrated in artificial saliva (within ∼6 s) and dissolved fully in water within 2 min. The antioxidant activity demonstrated dose-dependent, enhanced radical scavenging activity of NN/SBE-β-CD-ICs and NFs compared to free NN, with ∼50 % DPPH radical scavenging at 200 μM concentration. Overall, the synergistic approach of cyclodextrin complexation and electrospinning markedly improved the solubility, stability, and antioxidant potential of NN, offering a promising platform for the development of fast-dissolving oral delivery systems for hydrophobic bioactives.