Anesthetic-Eluting Contact Lens for Corneal Pain

由损伤或手术引起的急性角膜疼痛可能是严重的，使人虚弱。绷带隐形眼镜(BCL)可以减轻角膜疼痛，促进伤口愈合，但不能充分治疗疼痛。因此，也会开出口服阿片类药物。不幸的是，口服阿片类药物与副作用有关，并导致了全国范围内的阿片类药物流行；出于这些原因，眼科护理提供者和大多数患者更喜欢麻醉药。麻醉性滴眼液，如丁卡因，可以缓解角膜疼痛，但不能开出自我给药的处方，因为过度使用和滥用滴眼液可能会推迟伤口愈合。到目前为止，还没有一种眼麻醉药是FDA批准的自我给药。我们开发了一种麻醉剂洗脱绷带隐形眼镜(A-BCL)，通过引入一层完全包裹在典型水凝胶CL外围的药物聚合物薄膜，可以控制丁卡因的药物输送。可以通过改变药物聚合物膜的特性来调节释放轮廓。我们在兔身上的初步数据显示，疼痛刺激减少了长达30小时，没有证据表明伤口愈合受到影响。在我们实验室经验的基础上，这项应用的目标是通过以下目标完成必要的研究，使A-BCL进入首个人类临床试验：目标1：A-BCL的优化、有效性和特性。目的2：A-BCL的药物分布、安全性和生物相容性。目标3：实施GMP生产，IND前会议，并向FDA提交IND申请，进行使用A-BCL的首个人类临床试验。在目标1中，我们将丁卡因的释放时间从一天增加到两天，同时评估对正常兔眼的疗效。我们还将进行特性研究，以确保A-BCL符合可接受的绷带隐形眼镜参数。从这些研究中，我们将选择一种A-BCL制剂，该制剂将用于AIM 2中的药物分配、生物相容性研究，以及使用兔角膜上皮伤口愈合模型进行安全性研究。在目标3中，我们将完成A-BCL生产到GMP设施的技术转让。在监管顾问(ORA)的指导下，我们将举行IND前会议。一旦完成，我们将继续我们的生物兼容性研究，并完成IND申请，该申请将提交给FDA进行人类第一阶段I/II临床试验。如果这些努力取得成功，患者将首次获得严重角膜疼痛的非阿片类药物治疗。

Acute corneal pain from injury or surgery can be severe and debilitating. Bandage contact lenses (BCLs) mitigate corneal pain and promote wound healing, but do not sufficiently treat the pain. As a result, oral opioids are also prescribed. Unfortunately, oral opioids are associated with side effects and have contributed to the nationwide opioid epidemic; for these reasons eye care providers and most patients prefer narcotics. Anesthetic eye drops, such as tetracaine, can relieve corneal pain, but cannot be prescribed for self-administration due to the potential for delayed wound healing that has been attributed to overuse and abuse of the drops. To date, NO ocular anesthetics are FDA-approved for self-administration. We have developed an anesthetic-eluting bandage contact lens (A-BCL) that enables controlled drug delivery of tetracaine by introducing a thin drug-polymer film that is fully encapsulated within the periphery of a typical hydrogel CL. The release profile can be modulated by changing the characteristics of the drug polymer film. Our preliminary data in rabbits demonstrates up to 30 hours of reduced pain stimulation and no evidence of compromised wound healing. Building on our laboratory’s experience, the goal of this application is to complete the necessary studies to bring the A-BCL to a first-in-human clinical trial through the following Aims: Aim 1: Optimization, efficacy, and characterization of A-BCLs. Aim 2: Drug distribution, safety, and biocompatibility of A-BCLs. Aim 3: Implementation of GMP production, Pre-IND meeting, and submission of IND application to the FDA for a first-in-human clinical trial using A-BCLs. In Aim 1, we will increase the duration of tetracaine release from one to two days while evaluating efficacy in normal rabbit eyes. We will also conduct characterization studies to ensure the A-BCL meets acceptable parameters for bandage contact lenses. From these studies, we will choose a A-BCL formulation, which will be used in Aim 2 for drug distribution, biocompatibility studies, and safety using a rabbit model of corneal epithelial wound healing. In Aim 3, we will complete technology transfer of A-BCL production to a GMP facility. With guidance from regulatory consultants (ORA), we will conduct a Pre-IND meeting. Once this is complete, we will proceed with our biocompatibility studies and complete an IND application that will be submitted to the FDA for a first-in-human Phase I/II clinical trial. If these efforts are successful, patients will have, for the first time, an opioid-free treatment for severe corneal pain.