Injectable devices for sustained ocular drug delivery

该Healthcare Impact合作伙伴关系将使用我们以前发明的药物输送技术来开发新型的可注射设备，向眼睛内侧提供有针对性的、可控的和持续的药物输送。这些设备将解决两组患者未得到满足的临床需求。此外，我们将开发复杂的台式和眼睛药物释放的计算机模型，使我们能够加快开发速度，并减少在人体上使用这些设备所需的动物测试量。英国有超过570万人患有威胁视力的眼睛疾病。这些疾病包括糖尿病、黄斑变性和视网膜脱离。目前治疗视网膜脱离后瘢痕形成的最佳实践是向眼睛内注射硅油以取代玻璃体。有人提出，除了石油之外，持续的药物输送可能有助于减少疤痕的形成。我们以前开发了从硅油中实现受控、延长药物释放的技术，现在希望将这些技术应用于适合患者使用的硅油。其他威胁视力的疾病的治疗需要患者在多年内频繁地直接向眼睛内注射药物。这可能会给患者带来不适和不便，给医疗系统带来负担，在发展中国家是不可行的。有一小部分药物输送装置可以减少所需的注射次数，但这些装置必须在药物释放完成后移除，或者，如果装置是可降解的，持续时间不会比标准注射长得多。我们之前已经开发了将药物制成纳米颗粒的技术。我们将开发一种药物输送系统，该系统由纳米颗粒在一种材料中构建，当它被注射到眼睛中时，这种材料会形成凝胶。药物释放后，凝胶将降解为无毒成分。与现有设备相比，这一技术的优势在于，这项技术可以根据药物和剂量进行定制，而且由于使用纳米颗粒，可能会有更高的剂量。我们的两种输送装置都是可注射的，将改善患者的预后，特别是在发展中国家和晚期患者。我们的团队是多学科的，包括专门从事眼科生物材料和药物输送的学者。专门从事药物输送的临床眼科医生将确保我们的技术适合临床使用。我们还将与患者团体接触，他们将帮助我们制定发展战略。为了加速生产适合患者使用的设备的技术，我们与一家生产用于治疗视网膜脱离的硅油产品的公司建立了合作伙伴关系。凭借他们的专业知识，我们将能够确保我们在开发技术时包括某些关键方面，例如如何将生产规模从实验室扩大到适合商业用途，以及生成产品获得临床使用许可证所需的数据。另一家专门生产替代动物试验的模型的商业合作伙伴将帮助我们优化我们的模型，并向其他对减少动物使用感兴趣的组织推广它们的使用。我们将把我们基于硅油的药物释放技术应用于商业油类，确保所产生的产品具有适当的物理性质，以保持眼睛的功能性，无毒，并具有最佳的药物释放。我们还将开发我们的纳米颗粒系统，优化物理、药物释放和毒性特性。与此同时，我们将开发现有的台式和计算机模型，以便它们能够预测我们设备中的药物释放。

This Healthcare Impact Partnership will use drug delivery technologies previously invented by us to develop novel, injectable devices to provide targeted, controlled and sustained drug delivery to the inside of the eye. These devices will address unmet clinical needs in two groups of patients. In addition, we will develop sophisticated benchtop and computer models of drug release in the eye, to allow us to speed up development and reduce the amount of animal testing required to use the devices in humans. Over 5.7 million people in the UK are living with sight-threatening eye conditions. These include conditions that can develop as a result of diabetes, macular degeneration and retinal detachment. The current best practice for treatment of the scarring that can follow retinal detachment is injection of silicone oil into the eye to replace the vitreous. It has been proposed that, in addition to the oil, sustained drug delivery could help reduce the development of scarring. We have previously developed technology to achieve controlled, extended release of drugs from silicone oils, and now wish to apply these technologies to silicone oils that are suitable for use in patients. Treatment for other sight-threatening conditions requires patients to have frequent injections of drugs directly into the eye over many years. This can be uncomfortable and inconvenient for patients, places a burden on the healthcare system and is not feasible in developing countries. A small number of drug delivery devices that reduce the number of injections needed are available, but these must either be removed once the drug release is complete, or, if the device is degradable, do not last much longer than standard injections. We have previously developed technology to make drugs into nanoparticles. We will develop a drug delivery system constructed of nanoparticles inside a material that forms a gel when it is injected into the eye. After the drug has been released, the gel would degrade into non-toxic components. The advantages of this over existing devices are that this technology could be tailored in terms of the drug and dosing, and that higher doses will be possible due to the use of nanoparticles. Both of our delivery devices are injectable, and will improve patient outcomes, particularly in developing countries and patients that present late.Our team is multidisciplinary, including academics specialising in ophthalmic biomaterials and drug delivery. A clinical ophthalmologist specialising in drug delivery will ensure that our technologies are suitable for clinical use. We will also engage with patients groups, who will help inform our development strategy. In order to accelerate the technologies towards the production of devices that are suitable for use in patients, we have partnered with a company who manufacture silicone oil products used to treat retinal detachment. With their expertise, we will be able to ensure that we include certain crucial aspects as we develop our technologies, such as how to scale up manufacture from the laboratory to that suitable for commercial use, and the generation of data that is required for the products to gain a licence for clinical use. Another commercial partner specialising in the production of models to replace animal testing will help us optimise our models, and promote their use to other organisations who are interested in reducing animal use. We will apply our silicone oil-based drug release technology to commercially-available oils, ensuring the resulting product has appropriate physical properties to remain functional in the eye, is not toxic, and has optimal drug release. We will also develop our nanoparticle system, optimising physical, drug-release and toxic properties. At the same time, we will develop existing benchtop and computer models so that they will be able to predict drug release from our devices.