Mucoadhesive Electrospun Fibre-Based Technologies for Oral Medicine

Abstract

Oral disease greatly affects quality of life, as the mouth is required for a wide range of activities including speech, food and liquid consumption. Treatment of oral disease is greatly limited by the dose forms that are currently available, which suffer from short contact times, poor site specificity, and sensitivity to mechanical stimulation. Mucoadhesive devices prepared using electrospinning offer the potential to address these challenges by allowing unidirectional site-specific drug delivery through intimate contact with the mucosa and with high surface areas to facilitate drug release. This review will discuss the range of electrospun mucoadhesive devices that have recently been reported to address oral inflammatory diseases, pain relief, and infections, as well as new treatments that are likely to be enabled by this technology in the future.

Keywords: bioadhesion; drug delivery; electrospinning; infections; inflammation; local therapy; mucosa; oral cavity; pain relief.

Figure 1

Histological (left) and schematic (right) image of the buccal oral mucosa (histological image courtesy of Prof. Keith Hunter, Unit of Oral Pathology, University of Sheffield). Scale bar = 100 μm.

Figure 2

(A) Schematic diagram of typical electrospinning apparatus. A high voltage power supply injects charge into the metallic syringe tip, causing a polymer jet to be ejected towards the grounded collector plate. The jet dries during flight, depositing a nanofibre mesh. (B) Static collectors result in a random mesh of fibres; moving collectors can be used to produce aligned fibres; patterned collectors result in textured membranes. (C) Multiple needles in combination with a moving collector allow increased output or the production of mixed fibre types; coaxial needles allow the production of core-sheath fibres with multiple polymer domains; needleless spinnerets allow many polymer jets to be produced simultaneous to give increased output.

Figure 3

(A) Scanning electron microscopy image of fibres electrospun from a solution of Eudragit^® RS100 and poly(vinylpyrrolidone) in ethanol/water using a static collector. Scale bar = 100 μm. (B) Aligned polyhydroxyalkanoate blend fibres electrospun from chloroform using a rotating cylinder collector. Scale bar = 100 μm. Reproduced from [45], John Wiley & Sons Ltd., 2019. (C) Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) fibrous membranes with rectangular micropatterns electrospun from dichloromethane/methanol using a micropatterned static collector. Image courtesy of Dr Ílida Ortega Asencio, University of Sheffield. Scale bar = 1 mm.

Figure 4

Mucoadhesive Rivelin^® patches placed on the (A) gingiva, (B) lateral tongue, (C) buccal mucosa of a healthy human volunteer. Reproduced from [82], Elsevier Ltd., 2018.

Figure 5

Fabrication of multi-drug-loaded bilayer composite meshes using double-ring slit needleless spinneret. Yellow layer: curcumin-loaded PLLA nanofibre mesh; blue layer: diclofenac sodium-loaded PEO nanofibre mesh. Reprinted with permission from [41]. Copyright (2019) American Chemical Society.

Figure 6

Haematoxylin and eosin (H&E)-stained tissue sections and corresponding MALDI-MS images of porcine buccal mucosa exposed to dual-layer electrospun patches containing 3% (w/v) lidocaine HCl (m/z 235.1805 [M + Na]+; red) after 15 min, 1, and 3 h. The epithelium (blue) for each sample is shown using the epithelial marker lipid phosphatidylglycerol (34:1) (m/z 771.5140 [M + Na] +). The arrows in the H&E images show the position of the electrospun patch. Reproduced from [96]. Copyright (2019) American Chemical Society.