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胶膜，它可以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强西环素。特别是，我们将重点开发用于治疗口腔溃疡的胶膜，这是一个普遍存在的问题，影响着世界上许多人。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，一种强粘附的口腔内聚合物，它将使薄膜附着在溃疡病部位，并有一种惰性的背衬聚合物，以防止薄膜附着在其他口腔内表面。背面可以保护溃疡部位免受唾液和其他来源的刺激。其次，口服薄膜能够以可控的方式将两种药物组合从该薄膜中输送出去，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，包括用于将薄膜固定在口腔内的高度粘附层。一系列的胶片将被制作出来并评估其口腔粘连性。最有希望的影片进行药物装载试验。这种薄膜将由聚乙烯亚胺-儿茶酚组成，这种聚合物的灵感来自于贻贝和藤壶所使用的蛋白质，它们可以牢固地附着在物体表面，薄膜上有一层药物洗脱层和一层衬底。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具有柔韧性和弹性，从而不会因谈话或进食等过程而损坏。粘接层是这样的，除非用手指小心地拉开，否则薄膜不会从疼痛的表面移除。我们的初步研究表明，这些薄膜可以留在原地，直到被手指剥掉。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。利多卡因将被装载在薄膜中，洗脱动力学将被测定。除了利多卡因外，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。药物将通过与聚合物共溶来装载。释放的持续时间可以通过改变药物负荷和聚合物浓度来调整，这样释放可以持续至少几个小时。在我们的应用中，独特的方法是利用聚乙烯亚胺-儿茶酚作为粘合剂层，已知在潮湿条件下提供出色的粘合。在该项目结束时，Akina将开发一种新的口服药物洗脱胶膜，可以减轻与口腔溃疡相关的疼痛和痛苦。该项目的第二阶段将集中于动物研究，以显示口腔内膜进入人体临床应用的有效性。

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.