Novel Method for the Ocular Iontophoretic Delivery of Avastin and Lucentis

眼部电离子导入阿瓦斯汀和雷珠单抗的新方法

• 批准号: 7927575
• 负责人: William I Higuchi
• 金额: $ 21.4万
• 依托单位: ACIONT, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7927575
• 关键词: Acute; Address; Adverse effects; Aftercare; Age related macular degeneration; Application procedure; Area; Avastin; Back; Blindness; Businesses; Cataract; Choroidal Neovascularization; Chronic; Convection; Device Designs; Devices; Disease; Dose; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Electrophoresis; Electroporation; Endophthalmitis; Enhancers; Eye; Eye diseases; Foundations; Goals; Grant; Health; Health Care Costs; Healthcare Systems; In Vitro; Injection of therapeutic agent; Iontophoresis; Lasers; Lucentis; Magnetic Resonance Imaging; Measures; Methodology; Methods; Modeling; Nurses; Operating System; Operative Surgical Procedures; Ophthalmic examination and evaluation; Ophthalmologist; Oryctolagus cuniculus; Patients; Penetration; Pharmaceutical Preparations; Phase; Population; Posterior eyeball segment structure; Prevention; Procedures; Property; Prophylactic treatment; Quality of life; Retinal; Retinal Detachment; Risk; Safety; Schedule; Sclera; Specialist; Staging; Surface; System; Techniques; Time; Tissues; Topical application; United States; Vision; bevacizumab; catalyst; comparative; compliance behavior; conjunctiva; cost effective; density; electric field; improved; in vivo; lens; macromolecule; molecular size; novel; public health relevance; research study; treatment duration

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).

描述（由申请人提供）：离子噬菌体是一种使用轻度电流来增强药物通过组织的渗透的方法。我们的长期目标是开发能够将大分子抗VEGF剂传递到眼后段的visulex（R）眼部离子噬菌体装置： *一种安全的，无创的眼药输送方法，从而提高了患者的依从性。 *由护士，专业人士甚至患者操作的系统，使抗 AMD患者更容易获得VEGF疗法，从而改善了视力和生活质量 我们人口的大部分。 *对我们的健康C的成本效益是通过减少视网膜专家处理的复杂程序（即激光或手术程序）的需求来最大程度地减少系统的系统。 *可以通过合并或变化的离子噬菌体来调整抗VEGF治疗的剂量 参数（例如电流密度或治疗持续时间）；药物配方（例如合并 电流增强剂）；或电穿孔方法。 *在解决急性条件和 这些边界案例，例如AMD干燥形式的早期阶段，仅预防 保证抑制AMD的治疗措施。 *与经常解决慢性AMD治疗的频繁治疗相关的风险将小于IVT注射。 为了实现这一目标的概念证明，我们将以三个具体目标进行该项目： 1）优化Avastin和Avastin（R）的眼部输送系统的离子遗迹参数 体外的卢森蒂斯（R）。 2）研究药代动力学并评估眼睛的局部耐受性 兔子体内药物的离子遗迹给药。 3）建立avastin（R）和Lucentis（R）的经孢子离子噬菌体治疗 疾病治疗模型中的脉络膜新生血管化。 公共卫生相关性：我们的I期业务催化剂赠款建议使用轻度电流方法来开发非侵入性的，局部的眼药输送系统，允许在设备的医生办公室（类似于巩膜镜）中及时进行应用程序，该程序最终可以由护士或副群体执行。 与年龄相关的黄斑变性（AMD）是美国失明的主要原因。虽然抗VEGF化合物Avastin（R）和Lucentis（R）在治疗AMD的湿（急性，视力威胁）形式方面有效，但必须经常通过玻璃体内注射（IVT）注射它们。 IVT注射涉及许多严重的风险，包括视网膜脱离，内脑膜，IOP增加和白内障发生。频繁的眼内注射并不是病人友好的友好，并给我们的医疗保健系统带来了昂贵的程序，因为它们还花费了大量时间，这些视网膜专家的时间表在美国数量有限（不到2500）。