Drug-Eluting Intraocular Lens

药物洗脱人工晶状体

• 批准号: 8831326
• 负责人: Ken J Mandell
• 金额: $ 23.82万
• 依托单位: LAYERBIO, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8831326
• 关键词: Address; Adhesions; Adrenal Cortex Hormones; Affect; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotics; Aqueous Humor; Cataract; Cataract Extraction; Clinical Trials; Complex; Development; Dexamethasone; Diclofenac; Dose; Drug Formulations; Drug Kinetics; Ensure; Enzyme-Linked Immunosorbent Assay; Eye; Eyedrops; Health Services Accessibility; Histologic; Impaired cognition; Implant; In Vitro; Infection; Inflammation; Injection of therapeutic agent; Intraocular lens implant device; Kinetics; Lens (device); Letters; Manufacturer Name; Medical; Medical Device; Modeling; Operative Surgical Procedures; Optics; Oryctolagus cuniculus; Outpatients; Patients; Penetration; Performance; Pharmaceutical Preparations; Phase; Pilot Projects; Polymers; Positioning Attribute; Postoperative Care; Postoperative Period; Preparation; Procedures; Process; Property; Recovery; Regimen; Safety; Sampling; Silicon; Symptoms; Techniques; Technology; Testing; Thick; Time; Tissues; Toxicology; United States; base; biodegradable polymer; capsule; controlled release; experience; human subject; implantation; in vivo; lens; light transmission; medication compliance; molecular scale; novel; ocular surface; older patient; pre-clinical; prescription drug costs; prevent; public health relevance; socioeconomic disparity; success; surface coating

DESCRIPTION (provided by applicant): Cataract surgery involves replacement of an eye's natural lens with an artificial intraocular lens (IOL) and is the most common outpatient surgical procedure in the United States. Typical postoperative care for cataract surgery involves a complex regimen of eye drops for as long as four weeks following surgery that is challenging for patients to manage, particularly among elderly patients who often possess some degree of physical or cognitive impairment that limits their compliance with eye drop dosing. Patients also often experience tolerability issues with topical eye drops and suffer adverse symptoms. Furthermore, the efficiency of penetration of topical eye drops past the ocular surface to target tissue within the eye is extremely low, estimated to be < 3%. Consequently, eye drops have limited efficacy for treating inflammation, infection, and other cataract-surgery related condition. LayerBio Inc. therefore proposes to develop a drug-eluting IOL that automatically releases vital medications inside the eye after cataract surgery. This approach will enhance medication compliance, efficacy and tolerability of medication prescribed for cataract surgery. LayerBio will demonstrate the feasibility of a drug-eluting IOL achieving controlled and sustained release of an approved corticosteroid for treatment of postoperative inflammation with cataract surgery. Drug-eluting IOLs will be fabricated using LayerBio's proprietary LayerForm" coating technology. Standard IOLs implanted during cataract surgery will be treated with a transparent LayerForm" coating that automatically releases medication inside the eye obviating the need for postoperative eye drops. LayerBio coatings are based on a novel layer-by-layer (LbL) fabrication technique that enables assembly of drug molecules into an ultra-thin, biodegradable polymer coating with molecular-scale precision. Upon implantation, the coating gradually degrades in vivo releasing drugs directly to target tissue within the eye. During Phase I, LayerBio will demonstrate the feasibility for applying corticosteroid-based LbL coatings to actual IOLs and demonstrate robust performance both in vitro and in vivo. This effort will include optimization of drug loading and release in vitro, ensuring coating integrity after simulated in vitro surgical injections. In addition, pharmacokinetic and toxicology testing will be carried out n vivo in a rabbit model. These results will form the basis for Phase 2 efforts to further optimize coating performance, to scale the technology, and perform IND-enabling studies in preparation for clinical trials in human subjects.

描述（由申请人提供）：白内障手术涉及用人工体内镜头（IOL）替换眼睛的天然镜头，并且是美国最常见的门诊手术手术。白内障手术的典型术后护理涉及手术后四个星期的复杂眼滴治疗方案，这对于患者的管理具有挑战性，尤其是在经常患有某种程度的身体或认知障碍的老年患者中，限制了他们对眼部下降剂量的依从性。患者通常还会出现局部眼部掉落并患有不良症状的耐受性问题。此外，局部眼部掉落的效率超过眼表向眼睛内的组织靶向组织极低，估计<3％。因此，眼滴在治疗炎症，感染和其他白内障手术相关条件方面的疗效有限。因此，Layerbio Inc.建议开发一种药物洗脱的IOL，该IOL在白内障手术后自动释放眼睛内部的重要药物。这种方法将增强为白内障手术规定的药物的依从性，功效和耐受性。 Layerbio将证明使用药物洗脱的IOL可行性，并持续释放认可的皮质类固醇，以治疗白内障手术的术后炎症。将使用Layerbio专有的层形式“涂料技术”制造药物的IOL。在白内障手术过程中植入的标准IOL将通过透明的层面“涂层”涂层处理，该涂层可自动在眼睛内部释放药物，以证明对术后眼滴的需求。 Layerbio涂层基于一种新型的逐层（LBL）制造技术，该技术可以将药物分子组装到具有分子尺度精度的超薄的可生物降解的聚合物涂层中。植入后，涂层在体内逐渐降解，将药物直接释放到眼睛内的组织。在第一阶段，Layerbio将证明将基于皮质类固醇的LBL涂层应用于实际IOL的可行性，并在体外和体内表现出良好的性能。这项工作将包括优化药物负荷和体外释放，以确保模拟体外手术注射后涂层完整性。此外，在兔模型中将进行药代动力学和毒理学测试。这些结果将构成第2阶段努力的基础，以进一步优化涂料性能，扩展技术并进行辅助研究，以准备人类受试者的临床试验。