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控制型双药物释放黏附性电纺贴片在预防和治疗牙槽骨黏膜炎中的应用

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

机构信息

School of Clinical Dentistry, 19 Claremont Crescent, University of Sheffield, Sheffield S10 2TA, UK.

School of Clinical Dentistry, 19 Claremont Crescent, University of Sheffield, Sheffield S10 2TA, UK; Department of Chemistry, Brook Hill, University of Sheffield, Sheffield S3 7HF, UK.

出版信息

J Control Release. 2024 Dec;376:253-265. doi: 10.1016/j.jconrel.2024.09.048. Epub 2024 Oct 15.

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.

摘要

大约五分之一的人在智齿拔除后会出现牙槽骨炎(AO)。AO 的特征是拔牙窝内的血凝块丧失,导致感染和疼痛,导致反复去医院就诊,给医疗系统带来了巨大负担。目前的治疗方法并不理想;为了解决这个问题,我们开发了一种新型载药的粘膜粘附贴片,由双重静电纺丝的聚乙烯吡咯烷酮/聚(Eudragit RS100)(PVP/RS100)和聚(N-异丙基丙烯酰胺)(PNIPAM)纤维组成,由聚(ε-己内酯)(PCL)背衬层保护。这些贴片显示出长效镇痛剂布比卡因盐酸盐和抗炎药泼尼松龙的控制释放。贴片在组织工程化的牙龈粘膜上的局部应用表明,贴片释放的布比卡因和泼尼松龙在 24 小时后穿透上皮,实现了持续的组织渗透,布比卡因盐酸盐的渗透度为 54.8±3.3%,泼尼松龙的渗透度为 65.8±5.1%。释放后药物仍保持其功能;布比卡因盐酸盐显著(p<0.05)抑制了 SH-SY5Y 神经元细胞中藜芦碱诱导的细胞内钙离子流,而泼尼松龙显著降低了刺激的 THP-1 单核细胞中白细胞介素 6(2 倍;p<0.001)、CXCL8(5.1 倍;p<0.01)和 TNF-α(1.5 倍;p<0.001)的基因表达。总的来说,这些数据表明,双重静电纺丝贴片具有提供粘膜粘附覆盖物的潜力,以防止血凝块丢失,同时在拔牙部位提供止痛和抗炎治疗,以预防和治疗 AO。这项研究不仅为 AO 提供了未来的治疗途径,而且为牙周或口腔粘膜组织的药物输送装置的未来发展提供了有价值的见解。

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