Intra-Oral drug-eluting adhesive film

描述(申请人提供)：这项第一阶段研究的目标是开发一种口腔内粘附膜，它可以覆盖和保护各种口腔溃疡，并将低剂量的止痛剂利多卡因和抗炎多西环素输送到疼痛部位。特别是，我们将专注于开发用于治疗溃烂疮的粘附膜，这是一个普遍存在的问题，影响着世界各地的许多人。在这个项目中，我们介绍了开发口腔内膜的两个创新方面。首先，一种粘附性很强的口腔内聚合物，它将保持薄膜与溃烂部位的粘附性，并使用惰性支持聚合物防止薄膜粘连到口腔内的其他表面。背衬表面将保护溃烂部位免受唾液和其他来源的刺激。其次，口腔内药膜能够以受控的方式提供来自该药膜的两种药物组合，以减轻疼痛和痛苦。该项目的目标将通过以下两个具体目标来实现。第一个具体目标是开发一种新的薄膜配方，该配方由高度粘附层组成，用于将薄膜固定在口腔内。将开发一系列薄膜，并将对其口腔粘附性进行评估。最有希望的电影将进行药物加载测试。该膜将由聚乙烯亚胺-儿茶酚组成，这是一种聚合物，灵感来自贻贝和藤壶使用的蛋白质，以强烈附着在表面，带有药物洗脱层和背衬。这些层将由无毒和可溶于水的材料设计。这些薄膜将被设计成具有弹性和弹性，从而不会被说话或进食等过程损坏。粘合层是这样的，除非用手指小心地拉开，否则薄膜不会从酸痛的表面上移除。我们的初步研究表明，这些薄膜可以一直留在原地，直到被手指剥离。第二个具体目标是将药物加载到薄膜配方中，以便它们能够以受控的方式释放。利多卡因将被加载到薄膜中，洗脱动力学将在。除了利多卡因，一种抗炎的小剂量强力霉素也将被释放，以缓解与溃烂溃疡相关的红肿。药物将通过与聚合物共溶解来加载。这一释放持续时间将通过改变药物载量和聚合物浓度来调整，以便释放可以持续至少几个小时。在我们的应用中，唯一的方法是利用聚乙烯亚胺-邻苯二酚作为粘附层，众所周知，这种粘合层在潮湿条件下具有良好的粘附性。在这个项目结束时，Aina将开发一种新的口腔内药物洗脱粘附膜，可以减少与溃烂溃疡相关的疼痛和痛苦。该项目的第二阶段将重点放在动物研究上，展示口腔内膜进入人类临床应用的有效性。 公共卫生相关性：这项第一阶段研究的目标是开发一种口腔内粘附膜，它可以覆盖和保护各种口腔溃疡，并将低剂量的止痛剂利多卡因和抗炎多西环素输送到疼痛部位。这些薄膜将克服与目前的技术相关的问题，目前的技术通常以非本地化的方式或在短时间内输送药物。这项技术将缓解一个普遍存在的、通常无法治疗的问题。

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.