Alginate-based mucoadhesive nanofibrous system embedding resveratrol-loaded vesicles as a therapeutic platform for nasal disorders.

Oxidative stress and inflammation play a key role in the development and progression of several otorhinolaryngological disorders, including chronic rhinosinusitis and allergic rhinitis. Resveratrol (RSV), a natural polyphenol with antioxidant and anti-inflammatory properties, is a promising therapeutic candidate, although its clinical application is limited by poor aqueous solubility and rapid mucociliary clearance upon nasal administration. In this study, a mucoadhesive nanofibrous nasal patch based on sodium alginate and poly(ethylene oxide) embedding RSV-loaded phospholipid vesicles was developed using a green electrospinning process based entirely on aqueous solvents. Both systems were characterized in terms of morphology, dimensional properties, swelling behavior, mucoadhesion, drug release, and biological activity. The RSV vesicles showed nanoscale dimensions (∼93 nm) and high entrapment efficiency (∼88%). The combined system resulting from the incorporation of the RSV vesicles into the nanofibrous matrix exhibited remarkable swelling properties (up to ∼800%), enhanced mucoadhesion, and a more sustained RSV release profile compared with vesicles alone, highlighting the role of the alginate network as a diffusion-controlling matrix. In vitro studies in immortalized human keratinocytes confirmed excellent biocompatibility and enhanced antioxidant activity. Overall, this vesicles-in-nanofibers platform represents a promising strategy for the nasal delivery of RSV, potentially improving its residence time and therapeutic effectiveness in upper airway diseases associated with oxidative stress and inflammation.