Computer modelling of drug delivery to the macula

描述（由申请人提供）：我们建议开发和实现后眼中药物分布的计算机模型，并应用于经巩膜和玻璃体内递送系统。这项工作将建立在我们自己和他人的基础上，将提供一个定量的、预测性的工具来设计药物输送策略。由于年龄相关性黄斑变性的重要性和将药物递送到黄斑的巨大挑战，这项工作的重点将是预测从各种递送方法到黄斑的运输。要解决的具体问题将是预测各种来源的生物分布。玻璃体内注射是黄斑的主要递送途径，但由于各种原因，它没有吸引力。经巩膜分娩是有吸引力的，但未经证实。新的想法也在出现。我们的软件将能够预先筛选交付方式，并确定最有吸引力的. 从动物模型到人类。动物模型中的药物转运可能与人类中的药物转运显著不同，因为眼睛几何形状和生理学的种间差异。我们将为人类、兔子和猪开发单独的模型，从而能够根据动物实验预测人类的分娩。 维生素液化。药物递送实验通常在年轻动物中进行，但大多数AMD患者年龄相当大，因此经历了相当大的玻璃体液化。液化的玻璃体可能具有与完整玻璃体非常不同的运输特性，并且我们将探索这种差异如何影响生物分布。拟议的项目直接关系到人类健康，因为它有可能改善对眼后部疾病的治疗，特别是黄斑变性，这是老年人失明的主要原因。该项目将使用计算机模型来改进将药物输送到眼睛后部的策略。如果我们知道如何将新药送到受影响的区域，那么年龄相关性黄斑变性（老年人失明的主要原因）等疾病就可以得到更有效的治疗。拟议的项目将有助于利用现有数据和生物工程原则来确定和指导更好的交付方法。

DESCRIPTION (provided by applicant): We propose to develop and implement a computer model of drug distribution in the posterior eye, with application to transscleral and intravitreal delivery systems. This work, which will build on that of ourselves and others, will provide a quantitative, predictive tool to design drug delivery strategies. Because of the importance of age-related macular degeneration and the great challenges in delivering drug to the macula, the emphasis of this work will be on predicting transport to the macula from various delivery methods. Specific issues to address will be Prediction of biodistribution from various sources. Intravitreal injection is the major delivery route to the macula, but it is unattractive for various reasons. Transscleral delivery is appealing but unproven. New ideas are also emerging. Our software will be able to pre- screen delivery methods and identify the most attractive. Translation from animal models to humans. Drug transport in animal models may be markedly different from that in the human because of interspecies differences in eye geometry and physiology. We will develop separate models for human, rabbit, and pig, and we will thus enable prediction of delivery in humans based on experiments in animals. Vitreous Liquefaction. Drug delivery experiments are routinely performed in young animals, but most AMD sufferers are quite old and thus have experienced considerable vitreous liquefaction. The liquefied vitreous is likely to have very different transport properties from the intact vitreous, and we will explore how such differences could affect biodistribution. The proposed project relates directly to human health because of its potential to improve therapy for posterior eye diseases, especially macular degeneration, the leading cause of blindness in the elderly. The project will use computer models to improve strategies for delivering drugs to the back of the eye. Diseases such as age-related macular degeneration (the leading cause of blindness in the elderly) could be treated much more effectively if we knew how to get new drugs to the affected area. The proposed project will help use existing data and bioengineering principles to identify and guide better delivery methods.