I-Corps: Light responsive nanoparticle depot for controlled delivery of drugs to the eye

I-Corps：光响应纳米粒子库，用于受控地将药物输送到眼睛

• 批准号: 1558942
• 负责人: Rosibel Ochoa
• 金额: $ 5万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1558942&HistoricalAwards=false
• 关键词: Corps; Light; responsive; nanoparticle; depot

The only viable option for the treatment for many eye-related diseases involves the injection of drugs directly into the eye (intravitreal injections). These are difficult procedures for the doctor to perform and extremely uncomfortable for the patients receiving these treatments. As a result, there are issues with patient compliance and the risk of complications is high, both resulting in millions of dollars inefficiently spent on secondary medical costs. Furthermore, due to the fact that dosing is difficult to control, doctors will often use the maximum "safe" dose when treating these diseases to ensure efficacy, which unfortunately leads to strong and undesirable side effects from these potent drugs. Therefore, there is a need for a technology which can reduce the number of injections needed in the treatment regimen, as well as the ability to accurately control the amount of therapeutic drug introduced, while maintaining the same level of efficacy. These combined capabilities would relieve patients from unnecessary pain and suffering, reduce the chance for complications, and as a result, lead to increased patient compliance and improved clinical outcomes.One of the most severe of these eye diseases which require periodic intravitreal injections is the wet form of Age-related Macular Degeneration (wet AMD). Irreversible vision loss may occur if patients miss even one of their monthly prophylactic treatments. The proposed technology "AMDepot" is a drug delivery platform based on a proprietary, light-responsive polymer.Therapeutic drugs are loaded into the polymer in nanoparticle form, and released in a highly controlled manner upon exposure to light. This system allows the therapy to be administered repeatedly through the shining of a specific form of light into the eye, significantly reducing the number of intravitreal injections needed. The purpose of this study would be to investigate and validate the real-world need of a technology which can mitigate adverse effects from intravitreal injections by reducing the number of injections needed and replacing it with light-controlled dosing. While this technology could be useful in many disease settings, this I-Corps team will focus its initial efforts in the realm of wet AMD. To accomplish this, a detailed plan has been devised to interview some of the world-leading ophthalmologists at top U.S. eye centers, as well as AMD patients in several local support groups in Southern California to gain further insights into the problem and to validate the proposed hypotheses.

治疗许多眼部相关疾病的唯一可行选择包括将药物直接注射到眼睛中（玻璃体内注射）。这些是医生执行的困难程序，并且对于接受这些治疗的患者来说非常不舒服。因此，患者的依从性存在问题，并发症的风险很高，这两者都导致数百万美元的次级医疗费用无效。此外，由于剂量难以控制的事实，医生在治疗这些疾病时通常会使用最大“安全”剂量以确保疗效，这不幸地导致这些强效药物的强烈和不希望的副作用。因此，需要一种技术，其可以减少治疗方案中所需的注射次数，以及精确控制引入的治疗药物的量的能力，同时保持相同的功效水平。这些组合的能力将减轻患者不必要的疼痛和痛苦，减少并发症的机会，并因此导致增加患者的依从性和改善临床结果。这些需要定期玻璃体内注射的眼部疾病中最严重的一种是湿性形式的黄斑变性（湿性AMD）。如果患者错过了每月一次的预防性治疗，可能会发生不可逆的视力丧失。拟议技术“AMDepot”是一种基于专有光响应聚合物的药物递送平台。治疗药物以纳米颗粒形式装载到聚合物中，并在暴露于光时以高度受控的方式释放。该系统允许通过将特定形式的光照射到眼睛中来重复进行治疗，从而显著减少所需的玻璃体内注射次数。本研究的目的是调查和验证现实世界中对一种技术的需求，该技术可以通过减少所需的注射次数并用光控给药代替来减轻玻璃体内注射的不良反应。虽然这项技术在许多疾病环境中可能是有用的，但I-Corps团队将把最初的努力集中在湿性AMD领域。为了实现这一目标，我们制定了一个详细的计划，采访了美国顶级眼科中心的一些世界领先的眼科医生，以及南加州几个当地支持团体的AMD患者，以进一步了解问题并验证提出的假设。