Highly Mucoadhesive Sustainable Patches for Effective Treatment of Oral Lichen Planus

高度粘膜粘附可持续贴剂可有效治疗口腔扁平苔藓

• 批准号: EP/X026108/1
• 负责人: Ipsita Roy
• 金额: $ 60.12万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX026108%2F1
• 关键词: Highly; Mucoadhesive; Sustainable; Patches; Effective

Disruptions to the lining of the mouth can be extremely painful (e.g., mouth ulcers). Oral lichen planus (OLP) is a more widespread disease that can affect the lining of the mouth. It is a long-term condition, and whilst there are drugs available to treat it, there is currently no effective way to administer these drugs. The main agents used are steroid based and administered orally. Steroids are well known for side effects and the relatively high doses needed to treat can exacerbate the side effects found. One way to overcome these problems is to deliver the drug directly to the wound. However, because of the wet environment of the mouth and the highly mobile tissue, getting adherence to the mouth lining is a significant challenge. As part of a collaboration, we have obtained proof of concept data for a new highly adhesive polymer system (a family of polymers denoted as Polyhydroxyalkanoates (PHAs)) that is produced by bacteria, so is environmentally sustainable and have coupled this with a very simple chemistry (inspired by the polydopamine chemistry that mussel shells use to attach to wet surfaces) to further enhance the adhesiveness of this material that could be developed into a patch for highly effective treatment of OLP lesions. We have shown that the PHA itself is ~ 6.5 times more adhesive than Polycaprolactone (PCL), a frequently used medical polymer and utilising the polydopamine chemistry, we can further improve adhesiveness by 30-40%. The work we aim to undertake in this project is to make the patch as adhesive as possible, by optimising both the PHA polymer and polydopamine chemistry, to give the patch an adhesiveness that will last for up to 24 hours. We will also be developing some innovative processing to build in structures to release the steroid from the patch in a highly controlled way to give therapeutically relevant doses, only towards the mucosa, for the lifetime of the patch. In addition, we will be adding an antifungal agent to the patch to prevent the additional fungal infection that accompanies OLP. To test the development of our new patch system we will use in vitro models to allow rapid screening of materials/drug combinations, and these will be taken forward to test in an ex vivo model using salvaged (obtained as by products) oral mucosa tissue for the model. This will also enable us to reduce the animal testing that would be needed to move this technology towards clinical use. Final in vivo studies will be used to test drug release kinetics and inflammatory response.

口腔内壁的破坏可能是非常痛苦的（例如，口腔溃疡）。口腔扁平苔藓（OLP）是一种更广泛的疾病，可以影响口腔内壁。这是一种长期疾病，虽然有药物可用于治疗，但目前没有有效的方法来管理这些药物。使用的主要药物是基于类固醇的口服药物。类固醇是众所周知的副作用和治疗所需的相对较高的剂量可以加剧发现的副作用.克服这些问题的一种方法是将药物直接输送到伤口.然而，由于口腔的潮湿环境和高度移动的组织，粘附到口腔内层是一个重大的挑战。作为合作的一部分，我们获得了一种新型高粘性聚合物系统的概念验证数据（一种称为聚羟基链烷酸酯（PHA）的聚合物家族），所以是环境可持续的，并将其与一种非常简单的化学反应结合起来，（灵感来自贻贝贝壳用来附着在潮湿表面的聚多巴胺化学物质）以进一步增强该材料的可吸收性，该材料可被开发成用于高效治疗OLP损伤的贴片。我们已经表明，PHA本身的粘附性比聚己内酯（PCL）高约6.5倍，PCL是一种常用的医用聚合物，利用聚多巴胺化学，我们可以进一步提高30- 40%的粘附性。我们在该项目中的目标是通过优化PHA聚合物和聚多巴胺化学，使贴片尽可能具有粘性，使贴片具有持续长达24小时的粘性。我们还将开发一些创新的工艺，以建立结构，以高度受控的方式从贴片中释放类固醇，在贴片的使用寿命内仅对粘膜给予治疗相关剂量。此外，我们将在贴片中加入抗真菌剂，以防止OLP伴随的其他真菌感染。为了测试我们的新贴剂系统的开发，我们将使用体外模型来快速筛选材料/药物组合，并将这些材料/药物组合用于使用回收的（作为副产品获得的）口腔粘膜组织的离体模型中进行测试。这也将使我们能够减少将这项技术推向临床应用所需的动物试验。最终的体内研究将用于测试药物释放动力学和炎症反应。