Nanoporous Films for Ocular Drug Delivery

描述（由申请人提供）：该项目旨在通过创建用于持续眼内递送基于抗体的治疗剂以抑制血管内皮生长因子（VEGF）的平台来治疗年龄相关性黄斑变性（AMD）。该跨学科团队将设计和制造原型纳米多孔薄膜设备;建立药物装载技术和药物释放特性;并在体外和动物眼模型中完成临床前生物相容性和功能测试。与其他缓释技术不同，拟议的薄膜装置在功能上可调，以实现零级药物释放动力学，在几个月内实现平坦的药物释放曲线和严格的浓度范围。通过将药物隔离在装置内的下层储库层中，可以保护药物免受外部微环境的影响。这种负载和保护药物的能力是基于生物的疗法的关键，这些疗法通常会经历快速降解和从眼睛中清除。该计划中提出的装置设计将缓解眼部药物递送中固有的许多挑战，并提供眼部治疗药物递送的创新方法。 公共卫生相关性：视网膜疾病治疗的进展与眼部药物输送的进展密切相关。本文提出的眼内给药平台可以增强用于各种后部眼部疾病的眼科药物的给药和功效。我们建议使用可注射的纳米多孔薄膜装置，在几个月内提供具有零级动力学的药物释放，用于递送大分子和生物药物。

DESCRIPTION (provided by applicant): This project seeks to treat age related macular degeneration (AMD) by creating a platform for the sustained intra-ocular delivery of antibody-based therapeutic agents to inhibit vascular endothelial growth factor (VEGF). This interdisciplinary team will design and manufacture prototype nanoporous thin-film devices; establish drug loading techniques and drug release properties; and complete pre-clinical biocompatibility and functional testing in vitro and in animal eye models. Unlike other sustained release technologies, the proposed thin-film devices are functionally tunable to achieve zero-order drug release kinetics, attaining a flat drug release profile and a tight concentration range over several months. By sequestering drug in an underlying reservoir layer within the device, the drug can be protected from the external microenvironment. This ability to load and protect the drug is key for biologically-based therapies which often undergo rapid degradation and clearance from the eye. The device design proposed in this program will mitigate many challenges inherent in ocular drug delivery and provide an innovative approach to the delivery of ocular therapeutics. PUBLIC HEALTH RELEVANCE: Progress in therapeutics for retinal diseases is closely linked to advances in ocular drug delivery. The intra-ocular drug delivery platform proposed here can enhance the administration and efficacy of ophthalmologic drugs for a variety of posterior eye diseases. We propose the use of an injectable nanoporous thin film device to provide drug release with zero-order kinetics over several months, for the delivery of both large molecule and biologic drugs.