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

这项研究的背景是什么？这项研究的目的是开发一种新的、更有效的治疗口腔上皮异型增生(OED)的方法。OED每100人中就有2人受到影响，出现在口腔线条组织中，在那里呈现出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转变为口腔癌。OED的诊断方法是采集受影响区域的组织样本(活组织检查)，并在显微镜下进行检查。目前，对于如何管理或治疗牛津英语学习障碍，还没有达成共识。手术切除仍然是严重病变组织最常见的治疗形式。然而，到目前为止，还没有任何治疗方法被证明能有效地阻止OED发展为口腔癌。最近的实验研究报告称，一些现有的或新的化疗药物可能会干扰OED进展为癌症的方式，因此如果它们能够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涂抹到口腔内壁仍然具有挑战性，因为它的表面是潮湿的。由于唾液、吞咽、舌头和下巴运动的作用，凝胶、漱口水、乳膏和软膏的保留率很低。然而，使用一种名为静电纺丝的技术制造的材料的最新进展提供了开发一种贴片的可能性，这种贴片可以紧密地附着在口腔的衬里上，并直接将药物释放到使用该贴片的区域。这项研究将会取得什么成果？这项研究的目的是开发一种可以粘在口腔衬里上的粘性贴片，并释放出可以治疗OED的药物。我们将在实验室优化并严格测试该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。这些数据将为将这种类型的治疗推向临床试验提供极其有用的信息。为什么开发新的治疗方法很重要？牛津英语学习障碍转化为口腔癌的比率为20%。在英国，每年大约有12,500例头颈部癌症被诊断出来，确诊后5年的存活率仍然很低，只有59%，每年导致4000人死亡。在世界范围内，死亡更为普遍，口腔癌在最常见的癌症中排名第六。口腔癌在很大程度上是一种可以预防的疾病，早期发现和处理OED对避免癌症进展至关重要。目前的管理和治疗选择不充分，无法解决疾病的发展方式。开发一种更有效的治疗OED的方法有可能防止口腔癌的进展，最终拯救生命。这项研究将如何进行？静电纺丝是一种名为聚合物的化学物质在高压下从液体转化为细小纤维网状物的技术，这种网状物看起来像棉花糖。药物可以混合到聚合物溶液中，这样当电纺时，它们就会并入聚合物纤维中。然后，这些纤维可以制成补丁，类似于小石膏。我们已经开发出一种特殊的聚合物混合物，它能紧密地附着在口腔的衬里上，并在使用时提供药物。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，药物从贴片中释放的速度和数量。一旦药物从贴片中释放出来，我们将首先使用实验室培养的细胞和组织实验来评估它们在杀死或改变OED细胞方面的有效性。最后，我们将采用最有希望的含药贴片，并将这些贴片用于治疗患上实验性OED的大鼠，以便在进行临床试验之前确定这些治疗方法是否对活组织有效。

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.