Novel Method for the Ocular Iontophoretic Delivery of Avastin and Lucentis

描述(申请人提供)：离子导入是一种使用温和的电流来增强药物在组织中的渗透的方法。我们的长期目标是开发能够将大分子抗血管内皮生长因子药物输送到眼睛后部的Visulex(R)眼部离子导入设备： *一种安全、非侵入性的眼部给药方法，从而提高患者的依从性。 *由护士、辅助专业人员甚至病人自己操作的系统，使反 AMD患者更容易接受血管内皮生长因子治疗，从而改善视力和生活质量 我们人口中的更大比例。 *对我们的健康系统具有成本效益，最大限度地减少了对视网膜专家处理的复杂程序(即激光或外科程序)的需要。 *抗血管内皮生长因子疗法的剂量可以通过结合或改变离子导入来调整 参数(例如电流密度或治疗持续时间)；药物配方(例如 电渗透促进剂)；或电穿孔方法。 *改变AMD的治疗模式，包括应对急性疾病和 那些边缘病例，如干性AMD的早期阶段，只有预防 抑制AMD的治疗措施是有必要的。 *与经常治疗慢性AMD相关的风险将低于静脉注射。 为了实现这一目标的概念证明，我们将在三个具体目标下开展这一项目： 1)优化阿瓦斯丁和阿瓦斯丁的眼部给药系统的离子导入参数 Lucentis(R)体外试验。 2)药物动力学研究及局部耐受性评价 药物在兔体内的离子导入给药。 3)建立阿瓦斯丁(R)和Lucentis(R)的经巩膜离子导入治疗 疾病治疗模型中的脉络膜新生血管。 与公共健康相关：我们的第一阶段业务催化剂基金建议开发一种非侵入性、局部眼部给药系统，使用温和的电流方法，允许在医生办公室及时应用设备(类似于巩膜透镜)，最终可以由护士或辅助专业人员执行。 老年性黄斑变性(AMD)在美国是导致失明的主要原因。虽然抗血管内皮生长因子化合物阿瓦斯丁(R)和Lucentis(R)在治疗湿性(急性、威胁视力)型AMD方面有效，但它们必须经常通过玻璃体内注射(IVT)来使用。静脉注射涉及许多严重的风险，包括视网膜脱离、眼内炎、眼压升高和白内障形成。频繁的眼内注射对患者不友好，并为我们的医疗保健系统带来昂贵的程序负担，因为它们还占用了美国人数有限的视网膜专家(不到2500人)的大量时间。

DESCRIPTION (provided by applicant): Iontophoresis is a method of using a mild electrical current to enhance the penetration of a drug through tissue. Our long term goal is to develop the Visulex(r) ocular iontophoresis device capable of delivering large molecule anti-VEGF agents to the posterior segment of the eye: * A safe, noninvasive ocular drug delivery method, thereby improving patient compliance. * A system operated by nurses, paraprofessionals, or even patient themselves, making anti- VEGF therapy more accessible to AMD patients thereby improving vision and quality of life for a greater portion of our population. * Cost effective for our health c are system by minimizing the need for complicated procedures (i.e. laser or surgical procedures) handled by retinal specialists. * Dosing of anti-VEGF therapy can be adjusted by incorporating or varying iontophoresis parameters (e.g. current density or treatment duration); drug formulations (e.g. incorporation of electroosmosis enhancers); or electroporation methods. * Changing a treatment paradigm for AMD both in terms of addressing acute conditions and those borderline cases such as early stages of the dry form of AMD where only prevention treatment measures to inhibit AMD are warranted. * The risks associated with frequent treatments addressing chronic AMD therapy would be less than IVT injections. To achieve proof of concept of this goal, we will conduct this project under three specific aims: 1) To optimize the iontophoretic parameters for an ocular delivery system of both Avastin(r) and Lucentis(r) in vitro. 2) To study the pharmacokinetics and assess the local tolerance of the eye following iontophoretic administration of the drugs in vivo in rabbit. 3) To establish transscleral iontophoresis of Avastin(r) and Lucentis(r) for the treatment of choroidal neovascularization in a disease treatment model. PUBLIC HEALTH RELEVANCE: Our phase I business catalyst grant proposes to develop a non-invasive, topical ocular drug delivery system using a mild electrical current methodology allowing for a timely application procedure in the doctor's office of a device (resembling a scleral lens) which eventually can be performed by a nurse or paraprofessional. Age-related macular degeneration (AMD) is a leading cause of blindness in the United States. While anti-VEGF compounds Avastin(r) and Lucentis(r) are effective in the treatment of the wet (acute, sight threatening) form of AMD, they must be administered frequently by intravitreal (IVT) injections. IVT injections involve a number of serious risks including retinal detachment, endophthalmitis, increased IOP and cataractogenesis. Frequent intraocular injections are not patient friendly and burdens our health care system with expensive procedures as they also take up a great deal of time out of the schedules of retinal specialists who are limited in numbers in the United States (less than 2500).