Computer modelling of drug delivery to the macula

描述（由申请人提供）：我们建议开发并实现药物在后眼分布的计算机模型，并应用于经巩膜和玻璃体内给药系统。这项工作将以我们自己和其他人的工作为基础，将为设计药物递送策略提供定量的预测工具。由于老年性黄斑变性的重要性和给药到黄斑的巨大挑战，这项工作的重点将是预测从各种给药方法到黄斑的运输。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给药途径，但由于种种原因，它缺乏吸引力。经巩膜分娩很有吸引力，但未经证实。新的想法也在不断涌现。我们的软件将能够预先筛选交付方式，并确定最具吸引力。从动物模型到人类模型的转换。由于不同物种间眼睛几何和生理结构的差异，药物在动物模型中的转运可能与在人类模型中的转运明显不同。我们将分别开发人类、兔子和猪的模型，从而能够在动物实验的基础上预测人类的分娩。玻璃体液化。药物传递实验通常在幼龄动物中进行，但大多数AMD患者相当老，因此经历了相当大的玻璃体液化。液化玻璃体可能与完整玻璃体具有非常不同的运输特性，我们将探讨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，因为它有可能改善后眼病的治疗，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球后部的策略。如果我们知道如何让新药进入受影响的区域，像老年性黄斑变性（老年人失明的主要原因）这样的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理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.