Fabrication and characterization of zein/PVA nanofibers containing ferulic acid-loaded cyclodextrin metal-organic framework for enhanced sustained release and bioavailability.

Advanced delivery systems are crucial for overcoming the limitations of ferulic acid (FA), including its poor water solubility and stability. This study utilized γ-cyclodextrin metal-organic framework (γ-CD-MOF) to encapsulate FA, yielding FA-loaded γ-CD-MOF (FA@CD-MOF) nanocarriers, which were subsequently incorporated into zein/polyvinyl alcohol electrospun nanofibers to construct a dual-encapsulation system. Results showed that FA@CD-MOF exhibited an average particle size of 228.36 nm, and demonstrated efficient FA encapsulation with a loading capacity of 27.39% and encapsulation efficiency of 51.76%. The composite nanofibers exhibited enhanced thermal stability and moderate anti-swelling properties. In vitro release studies demonstrated that the γ-CD-MOF effectively suppressed initial burst release of FA, and led to a sustained release profile that conformed to the Fickian diffusion mechanism. Furthermore, the composite nanofibers exhibited long-lasting antioxidant activity owing to the protective effect (nano-in-nano) of the delivery system. Notably, in vitro digestion experiments showed that the bioavailability of FA in the nanofibers reached 74.66%, a 2.9-fold increase compared to free FA (26.11%). Cytotoxicity tests on Caco-2 cells supported the remarkable biocompatibility and biosafety of the developed delivery system. Collectively, this study presents a highly promising strategy utilizing γ-CD-MOF for the controlled delivery of FA, which significantly enhances its stability and bioavailability.