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）：离子电渗疗法是一种使用温和电流增强药物渗透组织的方法。我们的长期目标是开发Visulex（r）眼离子电渗装置，该装置能够将大分子抗VEGF药物输送到眼后段： * 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。 * 一个由护士、准专业人员甚至病人自己操作的系统， VEGF治疗更容易为AMD患者所接受，从而改善视力和生活质量， 我们人口的更大一部分。 * 通过最大限度地减少由视网膜专家处理的复杂程序（即激光或外科手术）的需要，为我们的健康提供成本效益。 * 抗VEGF治疗的剂量可以通过结合或改变离子电渗疗法来调整 参数（例如电流密度或治疗持续时间）;药物制剂（例如掺入 电渗增强剂）;或电穿孔方法。 * 改变AMD的治疗模式， 这些边缘性病例，如早期阶段的干性AMD， 需要抑制AMD的治疗措施。 * 与针对慢性AMD治疗的频繁治疗相关的风险将低于IVT注射。 为了实现这一目标的概念验证，我们将在三个具体目标下开展该项目： 1)为了优化Avastin（r）和Avastin（r）的眼部递送系统的离子电渗参数， Lucentis（r）体外试验。 2)目的：研究眼局部耐受性， 离子导入法给药的研究 3)目的建立安维汀（Avastin，r）和Lucentis（Lucentis，r）经巩膜电离子导入治疗青光眼的方法。 在疾病治疗模型中的脉络膜新血管形成。 公共卫生相关性：我们的第一阶段商业催化剂赠款建议开发一种非侵入性的，局部眼部药物输送系统，使用温和的电流方法，允许在医生办公室及时应用程序的设备（类似于巩膜透镜），最终可以由护士或准专业人员执行。 视网膜相关性黄斑变性（AMD）是美国失明的主要原因。虽然抗VEGF化合物Avastin（r）和Lucentis（r）在治疗湿性（急性，威胁视力）形式的AMD中是有效的，但它们必须通过玻璃体内（IVT）注射频繁施用。IVT注射涉及许多严重风险，包括视网膜脱离、眼内炎、IOP升高和白内障形成。频繁的眼内注射对患者不友好，并且给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数量有限的视网膜专家（少于2500人）的大量时间。