Electrospun thiolated nanofibrous mats loaded with Zataria multiflora nanoemulsions for treating recurrent aphthous stomatitis

Background and purpose: Recurrent aphthous stomatitis (RAS) is a common painful inflammatory disease of the oral mucosa for which only a few effective therapeutic options are available. In this work, a new bilayer mucoadhesive nanofibrous film was developed and characterized, incorporating a nanoemulsion loaded with Zataria multiflora (ZMF) essential oil (ZMF-EO) into a thiolated chitosan (TCS) matrix to offer local, sustained, and biocompatible therapy for RAS. Methods: In this study, nanoemulsions containing ZMF-EO were prepared and characterized, then incorporated into bilayer electros pun films made of TCS and a polycaprolactone backing layer. The films were evaluated for drug loading, swelling behavior, mechanical properties, in vitro release, ex vivo permeation, mucoadhesion, antimicrobial activity, cell compatibility, and wound-healing performance. Results: The ZN-B4 nanoemulsion showed high ZMF loading (98.6 ± 0.8%), nanoscale droplet size (80.9 ± 4.2 nm), and sustained 24-hour release (77.94 ± 4.69%). TCS-3 improved mucosal adhesion and controlled swelling. The F2 film, containing ZN-B4 and TCS-3, showed high drug loading (16.51 ± 1.08%), appropriate tensile strength (4.08 ± 0.93 MPa), ex vivo mucoadhesive strength (17.1 ± 1.9 g), sustained 24-hour drug release (55.32 ± 3.61%), enhanced buccal permeation (51.48%), acceptable biocompatibility (82.3 ± 11.4% cell viability), and complete wound closure within 48 h. Conclusion: The findings indicate that the ZMF bilayer nanofiber mat represents a promising therapeutic platform for RAS management. Combining herbal medicine with nanotechnology presents an opportunity for effective disease management and facilitates clinical translation.