Electrospun rutin/methyl-β-Cyclodextrin/pullulan nanofibers for neuroprotection in a zebrafish model of intracerebral hemorrhage.

Supramolecular engineering using cyclodextrins offers an effective strategy to enhance the solubility and efficacy of hydrophobic bioactive molecules. In this study, we have developed a rutin (RTN) inclusion complex (IC) incorporated pullulan (PL)-based nanofibrous system for the delivery of RTN, improving its solubility and efficacy. The IC was prepared via host-guest complexation of methyl-β-cyclodextrin (M-β-CD) with RTN, as confirmed by nuclear magnetic resonance (NMR) spectroscopy. Further, the developed IC was incorporated into the PL matrix to fabricate fast-dissolving electrospun nanofibers (PL/IC-NF). Solid state characterization using Fourier transform infrared (FTIR), powder X-ray diffraction (P-XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) demonstrated intermolecular interactions, reduced crystallinity, and incorporation of IC within PL nanofibrous matrix. The scanning electron microscopy (SEM) revealed uniform and bead-free fibers with smooth morphology. The IC incorporation remarkably enhanced the aqueous solubility of RTN (∼46-fold) and enabled its rapid disintegration (∼3 s). The in vivo evaluation in a zebrafish intracerebral hemorrhage (ICH) model demonstrated reduced hemorrhagic severity, oxidative stress, apoptosis, and inflammation, while protecting neuronal damage. Our study demonstrated that integrating supramolecular ICs with electrospun nanofibers offers an effective strategy to enhance the efficacy of poorly soluble nutraceuticals and represents a promising strategy for ICH intervention.