Topical Nanoparticles for CNV

描述（由申请人提供）：年龄相关性黄斑变性（AMD）是50岁以上成年人失明的主要原因。脉络膜新生血管（CNV）是眼部脉络膜层新血管的病理生成，是AMD致盲的主要原因。目前AMD的治疗管理远非最佳，需要在眼玻璃体腔内反复注射。这种反复给药除了给患者带来不便外，还可能导致视网膜脱离和眼内炎。因此，开发可通过诸如局部给药等相对安全的给药途径进行给药的给药系统的需求尚未得到满足。因此，本项目旨在研究使用NanoTrans纳米颗粒技术局部给药模型药物双氯芬酸的可行性，用于脉膜新生血管的管理。双氯芬酸是一种非甾体抗炎药（NSAID），它的专利已过期，允许它与专有的NanoTrans纳米颗粒技术一起用于产品开发。此外，双氯芬酸滴眼液目前已被批准用于人类使用，特别是用于治疗眼表面和眼前段的炎症，最大限度地减少了开发双氯芬酸纳米颗粒滴眼液的监管障碍。双氯芬酸抑制环氧化酶（COX）酶和炎症介质，包括血管内皮生长因子（VEGF），这是脉络膜新生血管病理的关键生长因子。然而，目前可用的双氯芬酸滴眼液配方不能将药物递送到眼后，使药物有效治疗脉络膜新生血管。本研究的目的是验证一种假设，即具有增强渗透性配体的纳米颗粒表面功能化可以增加双氯芬酸从滴眼液到眼后部的递送，从而提高激光诱导脉络膜新生血管模型的疗效。除了CNV治疗外，所提出的双氯芬酸纳米颗粒在治疗眼后部其他炎症性疾病方面也具有潜在价值。这项研究的发现和发展的技术可以潜在地外推到其他治疗眼后疾病的药物。

DESCRIPTION (provided by applicant): Age Related Macular Degeneration (AMD) is the leading cause of blindness in adults over 50 years. Choroidal neovascularization (CNV), the pathologic creation of new blood vessels in the choroid layer of the eye, is a principal cause of blindness due to AMD. Current therapeutic management of AMD is far from optimal and requires repeated injections in the vitreous cavity of the eye. Such repeated administrations, besides being inconvenient for the patient, might lead to retinal detachment and endophthalmitis. Thus, there is an unmet need to develop delivery systems which can be administered by relatively safer routes of administration such as topical dosing. Therefore, this project is aimed at investigating the feasibility of using a nanoparticle technology of NanoTrans for topical administration of a model drug diclofenac, for the management of choroidal neovascularization. Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) that is off patent, allowing its use in conjunction with proprietary NanoTrans nanoparticle technologies for product development. Further, diclofenac eye drops are currently approved for human use, especially for treating inflammation of the eye surface and the anterior eye segment, minimizing the regulatory hurdles in the development nanoparticle eye drops of diclofenac. Diclofenac inhibits cyclooxygenase (COX) enzymes and hence inflammatory mediators including vascular endothelial growth factor (VEGF), a key growth factor underlying the pathology of choroidal neovascularization. However, currently available eye drop formulations of diclofenac do not deliver the drug to the back of the eye in adequate amounts for the drug to be effective in treating choroidal neovascularization. The purpose of this study is to test the hypothesis that nanoparticles surface functionalized with a permeability enhancing ligand can increase diclofenac delivery from an eye drop to the back of the eye, resulting in improved efficacy in a laser induced choroid neovascularization model. Besides CNV treatment, the proposed diclofenac nanoparticles are of potential value in treating other inflammatory disorders of the back of the eye. The findings and technologies developed in this study can potentially be extrapolated to other therapeutic agents intended for treating disorders of the back of the eye. PUBLIC HEALTH RELEVANCE: Age related macular degeneration (AMD) is a disease of the back of the eye that can cause blindness. The available treatments require frequent injections into the eye, which is painful, inconvenient, and potentially damaging to the eye. The proposed project is aimed at the development of an eye drop dosage form based on nanoparticle technologies of NanoTrans for treating AMD. Use of nanoparticle technologies of NanoTrans are expected to improve drug delivery to the back of the from an eye drop. Such an approach avoids the pitfalls associated with invasive drug administrations. The proposed technologies are likely to benefit various drugs intended for treating diseases of the back of the eye.