Electrospun core-shell nanofibres embedding drug nanocrystals for long-acting mucosal delivery

Oral mucositis (OM) is a common and painful complication of cancer therapies, compromising oral functions and quality of life. Traditional local treatments are limited by rapid clearance, poor local drug availability, and frequent reapplication, highlighting the need for mucoadhesive polymeric platforms enabling localized and sustained drug delivery. In this study, naringenin-nanocrystals (NAR-NCs) were produced via wet media milling to enhance NAR solubility and dissolution and subsequently encapsulated into core-shell electrospun nanofibres (NFs), with a hydrophilic poly(vinyl alcohol) (PVA)/Sangelose® (SG) core for NAR-NC stabilization and a polycaprolactone (PCL) shell for controlled release. A mucoadhesive coating composed of ethyl cellulose (EC) and SG was applied to the NAR-NC_NFs to prolong mucosal residence, protect against mechanical stress, and facilitate buccal administration. NAR-NCs exhibited a mean hydrodynamic diameter of ∼280 nm, narrow size distribution, high stability over 10 days, and a 3.6-fold increase in saturation solubility compared to raw NAR. Core-shell NFs displayed uniform, bead-free morphology with clear core-shell architecture. NAR-NCs encapsulated within NFs preserved their size after fibres dissolution, within the 200-500 nm range, suitable for buccal application and maintained tensile properties comparable to unloaded NFs. Release studies demonstrated that NAR-NCs dissolved rapidly (∼45 min), NAR-NCs_core NFs provided controlled release over 6 h, and the complete NAR-NCs_NFs system prolonged drug release up to 72 h. The system also demonstrated preliminary anti-inflammatory properties, as confirmed by IL-8 enzyme-linked immunosorbent assay (ELISA). The EC/SG_NFs prototypes maintained normal human dermal fibroblasts (NHDF) viability above 95%, supporting their suitability as a mucoadhesive, mechanically robust and biocompatible platform for oral mucositis treatment.