Controlled dual drug release from adhesive electrospun patches for prevention and treatment of alveolar osteitis

Abstract

Approximately one in five individuals experience alveolar osteitis (AO) following wisdom tooth extraction. AO is characterised by loss of the blood clot from the tooth extraction socket leading to infection and pain, resulting in repeated hospital visits that impose a substantial burden on healthcare systems. Current treatments are sub-optimal; to address this we developed a novel drug-loaded mucoadhesive patch composed of dual electrospun polyvinyl pyrrolidone/Eudragit RS100 (PVP/RS100) and poly(N-isopropylacrylamide) (PNIPAM) fibres protected by a poly(ε-caprolactone) (PCL) backing layer. These patches demonstrated controlled release of the long-acting analgesic bupivacaine HCl and the anti-inflammatory drug prednisolone. Topical application of patches to tissue-engineered gingival mucosa showed that patch-released bupivacaine and prednisolone achieved sustained tissue permeation with 54.8 ± 3.3 % bupivacaine HCl and 65.8 ± 5.1 % prednisolone permeating the epithelium after 24 h. The drugs retained their functionality after release; bupivacaine HCl significantly (p < 0.05) inhibited veratridine-induced intracellular calcium flux in SH-SY5Y neuronal cells, while prednisolone significantly reduced gene expression of IL-6 (2-fold; p < 0.001), CXCL8 (5.1-fold; p < 0.01) and TNF-α (1.5-fold; p < 0.001) in stimulated THP-1 monocytes. Taken together, these data show that dual electrospun patches have the potential to provide a mucoadhesive covering to prevent blood clot loss while delivering pain relief and anti-inflammatory therapeutics at tooth extraction sites to prevent and treat AO. This study not only offers a future therapeutic pathway for AO but also contributes valuable insights into future advancements in drug delivery devices for periodontal or oral mucosal tissue.