Mathematical Modeling and Analysis of Ocular Fluid Dynamics and Transport Phenomena for Retinal Drug Delivery

视网膜药物输送的眼液动力学和传输现象的数学建模和分析

基本信息

批准号：
10002238
负责人：
REX A MOATS
金额：
$ 40.5万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10002238
关键词：
Affect Age Aging Animal Model Animals Area Biophysics Blindness Bolus Infusion Characteristics Chemicals Convection Coupled Data Deposition Diffusion Drug Delivery Systems Drug Transport Effectiveness Elderly Equation Evaluation Eye Fluorescence Gel Heterogeneity Human Humor Implant Individual Investigation Least-Squares Analysis Life Liquid substance Location Magnetic Resonance Imaging Measurement Measures Mechanics Membrane Methods Modeling Ophthalmology Outcome Outcomes Research Particulate Particulate Matter Permeability Pharmaceutical Preparations Pharmacology Pharmacotherapy Physics Physiological Physiological Processes Physiology Process Protocols documentation Research Retina Retinal Diseases Specific qualifier value System Techniques Testing Transport Process Visualization Vitreous humor Work age related base biophysical properties design drug distribution experience experimental study fluid flow follow-up in vivo macromolecule mathematical analysis mathematical model nanoparticle nanoparticulate particle predictive modeling solute theories

项目摘要

Project Summary The focus of this work is on the modeling and analysis of the eye with regard to of the transport of drugs through the vitreous humor to the retina. With retinal diseases being one of the common causes of blind- ness amongst the elderly, it is imperative that efficient and effective drug-delivery methods targeting the retina be developed. To minimize drug distribution to undesired locations, intravitreal delivery, especially with the use of implants, has gained prominence. In this regard, a thorough understanding of the ocular transport processes is necessary, and a comprehensive mathematical model for the ocular fluid dynamics and transport phenomena with application to retinal drug delivery would be a major positive step. Among the challenges include understanding the transport of mac-romolecular and particulate drugs together with the effect of partial liquefaction (syneresis) of the vitreous with age. The specific aims include: 1. Mathematical Analysis and Measurement of Ocular Transport Parameters. In order utilize the mathematical model for real-life drug delivery, the biophyisical parameters relevant to fluid flow and drug transport need to be accurately determined for various drug types. These include, for example, the diffusion coefficient of the vitreouus humor, the permebility of the membranes around the vitreous, and the hindrance evaluation that large molecules and particles experience in the vitreous. We shall carry this out with the known scientific techniques, as well as the new methods that we have recently developed. 2. Ocular Fluid Dynamics and Transport: Comprehensive Mathematical Model with Syneresis. The measurements that will be made in Task 1 will be implemented in a mathematical model which entails the various transport processes of the physiologically natural fluids in the system as well the intervening drugs, coupled with permeation into the retinal region. The relevant transport equations will be solved computationally and validated with careful experimentation (Task 3). The model will be applied to provide drug delivery rates as a function of the location of drug deposition, drug type, the eye topography (degree of liquefaction and location) and other transport parameters of the eye. 3. Validate the Modeling and Analysis with Experiments. Applications of the mathematical model will be made for intravitreal delivery using sustained-release macrmolecular implants in animal models for which the requisite biophysical properties will have been determined in Task 1. Syneretic conditions will be created mechanically (avoiding chemicals) to different levels with a variety of possible eye topographies. This will be followed up with the determination of required delivery levels, based on drug type and delivery method. To overcome potential issues between our model and the experimental data, we will begin animal model experimentation early in the second year, along with the ex vivo experiments in order to modify and validate our model.

项目概要这项工作的重点是对眼睛进行药物运输的建模和分析通过玻璃体到达视网膜。视网膜疾病是导致失明的常见原因之一老年人的健康状况，迫切需要针对老年人的高效、有效的药物输送方法视网膜得以发育。为了尽量减少药物分布到不需要的位置，玻璃体内给药，尤其是随着植入物的使用，它已经受到重视。对此，要深入了解眼科传输过程是必要的，并且眼部流体动力学的综合数学模型将转运现象应用于视网膜药物输送将是一个重大的积极步骤。之中挑战包括了解大分子和颗粒药物的运输以及随着年龄的增长，玻璃体部分液化（脱水收缩）的影响。具体目标包括： 1. 眼部传输参数的数学分析和测量。为了利用现实生活中药物输送的数学模型，与流体流动和药物相关的生物物理参数需要准确确定各种药物类型的转运。例如，这些包括玻璃体液的扩散系数、玻璃体周围膜的渗透性以及大分子和颗粒在玻璃体中经历的阻碍评估。我们将执行此使用已知的科学技术以及我们最近开发的新方法。 2.眼液动力学和传输：具有脱水作用的综合数学模型。任务 1 中进行的测量将在数学模型中实现，该模型需要系统中生理自然液体的各种运输过程以及干预药物，再加上渗透到视网膜区域。相关输运方程将得到求解计算并通过仔细的实验进行验证（任务 3）。该模型将应用于提供药物输送速率与药物沉积位置、药物类型、眼部地形（程度液化和位置）和眼睛的其他传输参数。 3. 通过实验验证建模和分析。数学模型的应用将在动物模型中使用缓释大分子植入物进行玻璃体内递送其必要的生物物理特性将在任务 1 中确定。协同条件将是通过机械方式（避免化学物质）创建不同级别的各种可能的眼睛地形。随后将根据药物类型和递送确定所需的递送水平方法。为了克服我们的模型和实验数据之间的潜在问题，我们将开始动物第二年年初进行模型实验，以及离体实验，以修改和验证我们的模型。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mathematical Model of Macromolecular Drug Transport in a Partially Liquefied Vitreous Humor.

部分液化玻璃体液中大分子药物转运的数学模型。

DOI：
10.1115/1.4053197
发表时间：
2022
期刊：
Journal of heat transfer
影响因子：
0
作者：
Khoobyar,Anahid;Penkova,AnitaN;Humayun,MarkS;Sadhal,SatwindarSingh
通讯作者：
Sadhal,SatwindarSingh

Mass diffusion coefficient measurement for vitreous humor using FEM and MRI.

使用 FEM 和 MRI 测量玻璃体液的质量扩散系数。

DOI：
10.1088/1757-899x/297/1/012024
发表时间：
2018
期刊：
IOP conference series. Materials science and engineering
影响因子：
0
作者：
Rattanakijsuntorn,Komsan;Penkova,Anita;Sadhal,SatwindarS
通讯作者：
Sadhal,SatwindarS

Analytical and Computational Modeling of Sustained-Release Drug Implants in the Vitreous Humor.

玻璃体液中缓释药物植入物的分析和计算模型。

DOI：
10.1115/1.4051785
发表时间：
2021
期刊：
Journal of heat transfer
影响因子：
0
作者：
Khoobyar,Anahid;Naghdloo,Amin;Penkova,AnitaN;Humayun,MarkS;Sadhal,SatwindarSingh
通讯作者：
Sadhal,SatwindarSingh

Diffusive Transport in the Vitreous Humor: Experimental and Analytical Studies.

玻璃体液中的扩散传输：实验和分析研究。