DEVELOPING PRE-CLINICAL MODELS TO OPTIMISE NANOPARTICLE-BASED DRUG DELIVERY FOR THE TREATMENT OF DIABETIC RETINOPATHY

糖尿病视网膜病变是一种与年龄有关的疾病，目前的治疗方法是通过控制药物直接输送到视网膜。虽然一些药物释放植入物是可用的，但标准的治疗包括频繁地向眼玻璃体注射药物。纳米医学、新药物疗法和药代动力学的进展为有效管理治疗提供了潜力。要实现这一目标，就需要能够表征纳米颗粒（NP）递送载体向细胞层扩散的模型。为了获得准确的浓度-响应关系，重要的是确定细胞实际暴露的NPs的局部浓度，而不是细胞培养/生物溶液介质中NPs的名义浓度。该项目将提供实时非侵入性无标签跟踪技术，该技术将用于通过玻璃体液体表征和量化NP运动，并使用光学显微镜与视网膜细胞直接相互作用。跟踪技术是基于Patterson和Whelan开发的“焦散技术”，Curran进一步将其用于体外应用。与该提案相关的平台技术和数据将直接有助于临床前筛选模型的生产，该模型可用于量化卡恩斯开发的基于纳米颗粒的眼科药物输送方案的效率。来自该模型的数据将用于设计药物输送模型（短期和长期）和优化纳米颗粒输送载体，以加强对年龄相关的糖尿病视网膜病变的治疗。该模型的发展也可以转化为其他相关的临床目标。

Diabetic retinopathy is an age-related condition that is currently managed by controlled delivery of drugs directly to the retina. Although some drug-releasing implants are available, standard treatment involves frequent injection of drugs into the vitreous of the eye. Advances in nanomedicine, new drug therapies and pharmacokinetics hold potential for effective management of the treatment. For this to be successful models are required which characterise the diffusion of nanoparticle (NP) delivery vehicles to the cell layer. To derive accurate concentration-response relationships, it is important to determine the local concentration of NPs to which the cells are actually exposed rather than the nominal concentration of NPs in the cell-culture/biological solution medium.This project will deliver real time non-invasive label-free tracking technologies that will be used to characterise and quantify NP motion through vitreous fluid and direct interactions with retinal cells using light microscopy. The tracking technology is based upon a "caustics technique" developed by Patterson and Whelan and further adapted by Curran for in vitro applications. The platform technologies and data associated with this proposal will directly contribute to the production of pre-clinical screening models that can be used to quantify the efficiency of nanoparticle based drug delivery regimes in ophthalmology developed by Kearns.Data derived from the model will be used to design drug delivery models (short and long term) and optimisation of nanoparticle delivery vehicles to enhance treatment for the age related condition of diabetic retinopathy. The development of the model can also be translated to other relevant clinical targets.