Intra-Oral drug-eluting adhesive film

描述（由申请人提供）：本I期研究的目的是开发一种口腔内粘合膜，可覆盖和保护各种口腔溃疡，并向溃疡部位输送低剂量的止痛利多卡因和抗炎多西环素。特别是，我们将专注于开发用于治疗口腔溃疡的粘合膜，这是一个影响世界各地许多人的普遍问题。在这个项目中，我们介绍了两个创新方面的发展口内电影。第一，强粘附性口腔内聚合物，其将保持膜与惰性背衬聚合物附接到溃疡部位，以防止膜粘附到其他口腔内表面。背衬表面将保护溃疡部位免受唾液和其他来源的刺激。第二，口腔内膜具有以受控方式从该膜递送两种药物组合以减少疼痛和痛苦的能力。该项目的目标将通过以下两个具体目标实现。第一个具体目标是开发一种新的膜制剂，其由用于将膜固定在口腔内的高粘附层组成。将开发一系列胶片，并对其颊侧牙槽骨进行评价。最有希望的膜进行载药测试。该薄膜将由聚乙烯亚胺-邻苯二酚组成，这是一种受贻贝和藤壶使用的蛋白质启发的聚合物，可牢固地粘附在表面，具有药物洗脱层和背衬层。这些层将由无毒且可溶于水的材料设计。这些薄膜将被设计成柔性和弹性的，以便不会被诸如说话或进食等过程损坏。粘合剂层使得膜不会从疼痛表面移除，除非用手指小心地拉开。我们的初步研究表明，薄膜可以留在原地，直到被手指剥离。第二个具体目标是将药物加载到膜制剂中，使得它们可以以受控的方式释放。将利多卡因加载到膜中，并在中测定洗脱动力学。除利多卡因外，还将释放一种抗炎、低剂量的强力霉素，以缓解与口腔溃疡相关的红肿。药物将通过将药物与聚合物共溶来装载。释放的持续时间将通过改变药物负载和聚合物浓度来调节，使得释放可以持续至少几个小时。在我们的应用中的独特方法是利用聚乙烯亚胺-邻苯二酚作为粘合剂层，已知其在潮湿条件下提供优异的粘合性。在该项目结束时，Akina将开发一种新的口腔内药物洗脱粘合膜，可以减少与口腔溃疡相关的疼痛和痛苦。该项目的第二阶段将专注于动物研究，以显示口腔内薄膜进入人类临床应用的功效。 公共卫生相关性：这项I期研究的目的是开发一种口腔内粘合膜，可以覆盖和保护各种口腔溃疡，并向溃疡部位提供低剂量的止痛利多卡因和抗炎多西环素。这些膜将克服与通常以非局部方式或短时间段递送药物的现有技术相关的问题。这项技术将为一个普遍存在且通常未经处理的问题提供缓解。

DESCRIPTION (provided by applicant): The objective of this Phase I study is to develop an intra-oral, adhesive film which can cover and protect various mouth sores and deliver low doses of pain relieving lidocaine and anti-inflammatory doxycycline to the sore site. In particular, we will focus on developing the adhesive film for treating canker sores, which is a ubiquitous problem affecting many people across the world. In this project, we introduce two innovative aspects in developing intra-oral films. First, a strongly adherent intra-oral polymer which will keep the film attached to the canker site with an inert backing polymer to keep the film from adhering to other intra-oral surfaces. The backing surface will protect the canker site from saliva and irritation from other sources. Second, the intra-oral film has the ability to deliver two-drug combination from this film in a controlled fashion to reduce pain and suffering. The objective of this project will be achieved through the following two specific aims. The first specific aim is to develop a new film formulation consisting of a highly adherent layer for securing the film inside the oral cavity. A series of films will be developed and will be evaluated for their buccal adhesiveness. The most promising films proceed to the drug loading test. The film will be comprised of polyethylenimine-catechol, a polymer inspired by the proteins used by mussels and barnacles to adhere strongly to surfaces, with a drug eluting layer and a backing layer. These layers will be designed from materials which are non-toxic and dissolvable in water. These films will be designed to be flexible and elastic so as to not be damaged by processes such as talking or eating. The adhesive layer is such that the film will not be removed from the sore surface unless carefully pulled away by fingers. Our preliminary study showed that the films could stay in place until being peeled away by fingers. The second specific aim is to load drugs into the film formulation so that they can be released in a controlled manner. Lidocaine will be loaded in the films and the elution kinetics will be determined in. In addition to lidocaine an anti-inflammatory, low dose doxycycline, will also be released to relieve the redness and swelling associated with canker sores. The drugs will be loaded by co-dissolving the drug in with the polymer. This duration of release will be adjusted by changing the drug loading and the polymer concentration so that the release can last for at least several hours. The unique approach in our application is to utilize polyethylenimine-catechol as the adhesive layer that is known to provide excellent adhesion under wet conditions. At the end of this project, Akina will develop a new intra-oral, drug eluting, adhesive film that can reduce pain and suffering associated with canker sores. Phase II of this project will focus on animal studies showing the efficacy of the intra-oral film to move into the human clinical applications. PUBLIC HEALTH RELEVANCE: The objective of this Phase I study is to develop an intra-oral, adhesive film which can cover and protect various mouth sores and deliver low doses of pain relieving lidocaine and anti-inflammatory doxycycline to the sore site. These films will overcome problems associated with current technology which generally delivers medication in a non-localized manner or for a short period of time. This technology will provide relief for a ubiquitous and generally untreated problem.