ICF: The development of a chemotherapeutic containing mucoadhesive patch for the treatment of oral epithelial dysplasia

ICF：开发含有粘膜粘附贴剂的化疗药物，用于治疗口腔上皮发育不良

• 批准号: MR/Y000234/1
• 负责人: Thomas Howe
• 金额: $ 44.97万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY000234%2F1
• 关键词: ICF; development; chemotherapeutic; containing; mucoadhesive

What is the context of the research?This research is aimed at developing a new and much more effective treatment for a disease called oral epithelial dysplasia (OED). OED affects 2 in every 100 people, and occurs in the tissue that lines the mouth where it presents as white or red regions that cannot be wiped away. Over time, these affected areas have the potential to turn into mouth cancer. OED is diagnosed by taking a tissue sample (biopsy) of the affected area and examining it under a microscope. Currently there is no consensus about how to manage or treat OED. Surgical removal remains the most common form of treatment for severely affected tissue. However, to date, no treatment has proven effective at stopping OED from progressing to mouth cancer. Recent experimental studies have reported that some existing or new chemotherapeutic drugs have the potential to interfere with the way OED progresses to cancer and so might be used as new treatments for people with OED, if they can be applied to the affected mouth tissue. Unfortunately, applying drugs to the lining of the mouth with any medication remains challenging because of its wet surface. Retention of gels, mouthwashes, creams and ointments is poor due to the actions of saliva, swallowing, and tongue and jaw movements. However, recent advances in materials made using a technique called electrospinning offers the potential to develop a patch that can adhere tightly to the lining of the mouth and release drugs directly to the area to which it is applied. What will this research achieve?The aim of this research is to develop an adhesive patch that can stick to the lining of the mouth and release drugs that can treat OED. We will optimise and rigorously test the effectiveness and safety of the system in the laboratory. We will also study how these drugs affect OED cells within tissues and how this facilitates treatment. These data will provide extremely useful information to take this type of treatment forward to clinical trials. Why is the development of new treatments important?The rate at which OED turns into oral cancer is 20%. Approximately 12,500 cases of head and neck cancer are diagnosed each year in the UK, survival rates remain poor at 59% 5 years after diagnosis, causing 4,000 deaths a year. Worldwide, deaths are more prevalent with mouth cancer placed as the 6th most common cancer. Mouth cancer is a largely preventable disease with early detection and management of OED critical to avoiding cancer progression. Current management and treatment options are inadequate and fail to address how the disease develops. Developing a more effective treatment for OED has the potential to prevent progression to mouth cancer, ultimately saving lives. How will the research be conducted?Electrospinning is a technique whereby chemicals called polymers are turned from a liquid into a fine fibre mesh that looks similar to candyfloss, using a high electrical voltage. Drugs can be mixed into the polymer solution so that they are incorporated into the polymer fibres when electrospun. These fibres can then be made into patches, similar to a small plaster. We have developed a special blend of polymers that adhere tightly to the lining of the mouth and deliver drugs when applied. Here, we will develop and optimise the production of new patches to contain a number of drugs that will specifically target OED cells. We will measure how quickly and how much of the drugs are released from patches over time. Once the drugs are released from the patches, we will assess their effectiveness at either killing or altering OED cells, firstly using experiments on cells and tissues cultured in the laboratory. Finally, we will take the most promising drug-containing patches and use these to treat rats that have developed experimental OED in order to determine if these treatments work on living tissue before moving towards clinical trial experiments.

研究的背景是什么？这项研究的目的是开发一种新的，更有效的治疗称为口腔上皮发育不良（OED）的疾病。每100人中就有2人受OED的影响，OED发生在口腔组织中，表现为无法擦除的白色或红色区域。随着时间的推移，这些受影响的区域有可能变成口腔癌。OED的诊断方法是取受影响区域的组织样本（活组织检查），并在显微镜下检查。目前，关于如何管理或治疗OED还没有达成共识。手术切除仍然是最常见的治疗形式严重影响组织。然而，到目前为止，还没有任何治疗方法被证明可以有效地阻止OED发展为口腔癌。最近的实验研究报告说，一些现有的或新的化疗药物有可能干扰OED发展为癌症的方式，因此如果它们可以应用于受影响的口腔组织，可能会被用作OED患者的新治疗方法。不幸的是，将药物与任何药物一起应用于口腔内壁仍然具有挑战性，因为其表面潮湿。由于唾液、吞咽、舌头和下颌运动的作用，凝胶、漱口水、乳霜和软膏的保留很差。然而，最近使用一种名为静电纺丝的技术制造的材料取得的进展，为开发一种可以紧紧粘附在口腔内壁并将药物直接释放到其应用区域的贴片提供了可能性。 这项研究将取得什么成果？这项研究的目的是开发一种可以粘附在口腔内壁并释放治疗OED药物的粘合剂。我们将在实验室优化并严格测试系统的有效性和安全性。我们还将研究这些药物如何影响组织内的OED细胞，以及这如何促进治疗。这些数据将提供非常有用的信息，将这种类型的治疗推向临床试验。为什么开发新的治疗方法很重要？OED转化为口腔癌的几率是20%。在英国，每年大约有12，500例头颈癌被诊断出来，诊断后5年的生存率仍然很低，为59%，每年造成4，000人死亡。在世界范围内，死亡率更高，口腔癌是第六大最常见的癌症。口腔癌是一种在很大程度上可以预防的疾病，早期发现和管理OED对避免癌症进展至关重要。目前的管理和治疗方案是不够的，未能解决疾病的发展。开发一种更有效的治疗OED的方法有可能阻止口腔癌的进展，最终挽救生命。 研究将如何进行？静电纺丝是一种利用高电压将一种叫做聚合物的化学物质从液体变成一种看起来像棉花糖的细纤维网的技术。药物可以混合到聚合物溶液中，以便在静电纺丝时将它们掺入聚合物纤维中。然后，这些纤维可以制成补丁，类似于一个小石膏。我们开发了一种特殊的聚合物混合物，可以紧密粘附在口腔内壁，并在应用时释放药物。在这里，我们将开发和优化新贴片的生产，以包含一些专门针对OED细胞的药物。我们将测量随着时间的推移，药物从贴剂中释放的速度和数量。一旦药物从贴片中释放出来，我们将评估它们杀死或改变OED细胞的有效性，首先使用实验室培养的细胞和组织进行实验。最后，我们将采取最有希望的含药物的贴片，并使用这些贴片治疗已经开发出实验性OED的大鼠，以确定这些治疗方法是否对活组织有效，然后再进行临床试验实验。