Topical Nanoparticles for CNV

描述(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)是眼部脉络膜层新生血管的病理性生成，是AMD致盲的主要原因。目前AMD的治疗方法远远不是最理想的，需要在眼睛的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，开发可以通过相对安全的给药途径(如局部给药)给药的递送系统的需求尚未得到满足。因此，本项目旨在研究使用纳米转运体纳米颗粒技术局部给药模型药物双氯芬酸用于脉络膜新生血管治疗的可行性。双氯芬酸是一种非类固醇抗炎药(NSAID)，已过专利，允许与专利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被批准用于人类，特别是用于治疗眼表和眼前节的炎症，最大限度地减少了开发双氯芬酸纳米颗粒滴眼液的调节障碍。双氯芬酸抑制环氧合酶(COX)酶，从而抑制包括血管内皮生长因子(VEGF)在内的炎症介质，血管内皮生长因子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足够多地输送到眼后，使其在治疗脉络膜新生血管方面有效。这项研究的目的是验证这样一个假设，即表面具有通透性增强配体的纳米颗粒可以增加双氯芬酸从眼药水到眼后的释放，从而在激光诱导的脉络膜新生血管模型中提高疗效。除了CNV治疗外，建议的双氯芬酸纳米粒在治疗眼后部其他炎症性疾病方面也有潜在价值。这项研究中开发的发现和技术可能会外推到其他旨在治疗眼后部疾病的治疗剂。 公共卫生意义：老年性黄斑变性(AMD)是一种眼后部疾病，可导致失明。现有的治疗方法需要频繁地在眼睛内注射，这是痛苦、不方便的，并可能对眼睛造成损害。拟议的项目旨在开发一种基于NanoTrans纳米颗粒技术的滴眼剂剂型，用于治疗AMD。纳米传输的纳米颗粒技术的使用有望改善药物从滴眼液到背部的输送。这种方法避免了与侵入性药物管理相关的陷阱。拟议中的技术可能会使旨在治疗眼后部疾病的各种药物受益。

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.