Large-scale and rapid preparation of nanofibrous meshes and their application for drug-loaded multilayer mucoadhesive patch fabrication for mouth ulcer treatment.

Electrospinning provides a simple and convenient method to fabricate nanofibrous meshes. However, the nanofiber productivity is often limited to laboratory scale, which cannot satisfy the requirements of practical application. In this study, we developed a novel needleless electrospinning spinneret based on a double ring slit to fabricate drug loaded nanofibrous meshes. In contrast to conventional single-needle electrospinning spinneret, our needless spinneret can significantly improve nanofiber productivity due to the simultaneous formation of multiple jets during electrospinning. Curcumin loaded poly (L-lactic acid) (PLLA) nanofiber meshes with various concentrations and large scale were manufactured by employing our developed needleless spinneret-based electrospinning device. We systematically investigated the drug release behaviors, antioxidant properties, anti-inflammatory attributes, and cytotoxicity of the curcumin loaded PLLA nanofibrous meshes. Furthermore, a bilayer nanofibrous composite mesh was successfully generated by electrospinning curcumin loaded PLLA solution and diclofenac sodium loaded poly(ethylene oxide) solution in a predetermined time sequence, which revealed potent anti-bacterial properties. Subsequently, novel mucoadhesive patches were assembled by combining the bilayer composite nanofibrous meshes with (hydroxypropyl)methyl cellulose-based mucoadhesive film. The multi-layered mucoadhesive patch had excellent adhesion properties on the porcine buccal mucosa. Overall, our double ring slit spinneret can provide a novel method to rapidly produce large scale drug-loaded nanofibrous meshes to fabricate mucoadhesive patches. The multiple layered mucoadhesive patches enable the incorporation of multiple drugs with different targets of action, such as analgesia, anti-inflammatory, and anti-microbial compounds, for mouth ulcer or other oral disease treatment.