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.

这项研究的背景是什么？这项研究旨在为一种称为口腔上皮性发育不良（OED）的疾病开发一种新的，更有效的治疗方法。 OED每100人中有2人，并且发生在将其显示为无法擦除的白色或红色区域的嘴的组织中。随着时间的流逝，这些受影响的地区可能会变成口腔癌。 OED通过采用受影响区域的组织样品（活检）并在显微镜下进行检查来诊断OED。目前，如何管理或治疗OED尚无共识。手术切除仍然是严重影响组织的最常见治疗形式。但是，迄今为止，尚无治疗能够有效阻止OED发展到口腔癌。最近的实验研究报告说，某些现有或新的化学治疗药物可能会干扰OED发展为癌症的方式，因此，如果可以将其应用于受影响的口腔组织，则可以用作OED患者的新治疗方法。不幸的是，由于其潮湿的表面，将药物涂在口腔上的嘴中仍然具有挑战性。由于唾液，吞咽，舌头和下巴动作的作用，凝胶，漱口水，面霜和药膏的保留差。但是，使用一种称为静电纺丝的技术产生的材料的最新进展为开发一个可以紧密粘附在口腔内衬并直接释放到施用区域的斑块的斑块中的潜力。 这项研究将实现什么？这项研究的目的是开发一种粘合剂，该粘合剂可以粘在口腔内，并释放可以治疗OED的药物。我们将优化并严格测试系统在实验室中的有效性和安全性。我们还将研究这些药物如何影响组织中的OED细胞以及该药物如何促进治疗。这些数据将提供极为有用的信息，以将这种类型的治疗转发到临床试验。为什么新疗法的发展很重要？在英国，每年诊断出大约12,500例头颈癌病例，诊断后5年59％的生存率仍然很差，每年造成4,000例死亡。在全球范围内，由于将口腔癌视为第六个最常见的癌症，死亡更为普遍。口腔癌是一种在很大程度上可以预防的疾病，对避免癌症进展至关重要的OED进行了早期检测和管理。当前的管理和治疗选择不足，无法解决该疾病的发展方式。为OED开发更有效的治疗方法有潜力防止进展为口腔癌，最终挽救生命。 该研究将如何进行？静电纺丝是一种使用高电压，将称为聚合物的化学物质从液体转变为看起来与Candyfloss的细纤维网。可以将药物混合到聚合物溶液中，以便在电气传播时将它们掺入聚合物纤维中。然后可以将这些纤维制成斑块，类似于小石膏。我们开发了一种特殊的聚合物混合物，这些聚合物紧密地粘在口衬上并在施用时输送药物。在这里，我们将开发并优化新斑块的生产，以包含许多将专门针对OED细胞的药物。随着时间的流逝，我们将衡量从斑块中释放出多少药物的速度和多少药物。一旦药物从斑块中释放出来，我们将评估它们在杀死或改变OED细胞方面的有效性，首先使用实验室中培养的细胞和组织进行实验。最后，我们将采用最有希望的含药物斑块，并使用这些斑块来治疗开发实验性OED的大鼠，以确定这些治疗方法在朝着临床试验实验迈进之前是否在生物组织中起作用。