Efficacy of the Microsphere-Thermo-Responsive Hydrogel Ocular Drug Delivery System

微球热响应水凝胶眼部给药系统的功效

基本信息

批准号：
9099053
负责人：
JENNIFER J Kang-Mieler
金额：
$ 41.99万
依托单位：
ILLINOIS INSTITUTE OF TECHNOLOGY
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：
2016-04-01 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9099053
关键词：
Address Adverse effects Affect Age related macular degeneration Animal Model Avastin Biocompatible Materials Biodegradable microsphere Blood Vessels Bolus Infusion Cataract Choroidal Neovascularization Clinical Clinical Research Clinical Trials Comparative Study Data Devices Diabetic Retinopathy Disease Dose Drug Delivery Systems Electroretinography Emulsions Encapsulated Endophthalmitis Endothelial Cells Family member Frequencies Glycolates Goals Healthcare Systems Hemorrhage Histology Hydrogels Image In Vitro Injectable Injection of therapeutic agent Knowledge Lasers Lucentis Measures Methods Microspheres Mind Mitogens Monitor Needles One-Step dentin bonding system Ophthalmoscopes Optical Coherence Tomography Patients Pharmaceutical Preparations Posterior eyeball segment structure Proteins Regimen Retinal Retinal Detachment Retinal Perforations Rodent Model Scanning Site System Techniques Technology Testing Therapeutic Effect Time Translations Treatment Efficacy Vascular Diseases Vascular Endothelial Growth Factors Vascular Permeabilities Visual Acuity Work angiogenesis base bevacizumab biomaterial compatibility blood flow measurement clinical practice comparative efficacy controlled release conventional therapy efficacy testing imaging modality in vitro Model in vivo in vivo Model public health relevance ranibizumab response treatment trial

项目摘要

DESCRIPTION (provided by applicant): Recently employed intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is a very promising treatment for the wet form of age-related macular degeneration and diabetic retinopathy. While the therapeutic effects are positive, a major drawback is that this treatment must be repeated every four to six weeks. This is not a desirable treatment method as it is associated with several inherent complications. No currently available device can deliver anti-VEGF in a sustained manner. Hence, there is a great need for a relatively non-invasive delivery system that is more effective than the current clinical regimen. Recently, we have developed a biodegradable microspheres, thermo-responsive hydrogel ocular drug delivery system. Biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres are produced using our modified double emulsion technique providing a better microenvironment for protein-based pharmacological agents. The thermo-responsive hydrogel is a safe, effective, and injectable biomaterial that is used to encapsulate and release various agents. The hydrogel will be used to confine the microspheres to a specific delivery site. We have established both a controlled sustained release of anti-VEGF for a period of 6 months and excellent biocompatibility of the proposed drug delivery system. The overall goal of this proposal is to demonstrate the efficacy of our proposed drug delivery in both in vitro and in vivo systems and by comparing to the conventional therapy. The hypothesis is that a sustained controlled anti-VEGF release over a prolong period of ~6 months will be as effective, if not more effective, as the conventional therapy. The goal of Specific Aim 1 is to quantitatively compare the efficacy and bioactivity of the proposed drug delivery system to the conventional therapy in its ability to suppress angiogenic responses in both in vitro and in vivo models. Specific Aim 1 will be accomplished in two parts: 1a testing bioactivity of released anti-VEGF agent in an in vitro model and 1b comparing the bioactivity and treatment efficacy via time-released anti-VEGF agents to conventional treatment in a laser-induced choroidal neovascularization (CNV) rodent model. The goal of Specific Aim 2 is to measure long-term efficacy and monitor for potential side effects, if any, of the proposed drug delivery system in an in vivo model. Long-term efficacy and potential side effects will be monitored through electroretinogram (ERG) responses, scanning laser ophthalmoscope (SLO)-vascular imaging blood flow measurements, spectral- domain optical coherence tomography (SD-OCT) and histological examination (at endpoint) in both control and treated groups. Widespread clinical use of anti-VEGF necessitates a practical and effective delivery method to the posterior segment of the eye. The knowledge gained in this proposal will bring this technology one step closer to translation into the clinical practice. We believe that our drug delivery system will provide a practical and effective method to deliver anti VEGF agents. The system will have a significant impact on the current healthcare system by reducing the frequency of injections and providing benefits of sustained treatment.

描述（由申请人提供）：最近采用的玻璃体内抗血管内皮生长因子（抗VEGF）疗法是治疗湿性年龄相关性黄斑变性和糖尿病性视网膜病的一种非常有前途的治疗方法，虽然治疗效果是积极的，但主要是。令人犹豫的是，这种治疗必须每四到六周重复一次，这不是一种理想的治疗方法，因为它与几种固有的并发症有关，因此，存在一种持续的抗 VEGF 治疗方法。非常需要一种比目前临床更有效的相对无创的输送系统最近，我们开发了一种可生物降解的微球，热响应水凝胶眼部药物递送系统，采用我们改进的双乳液技术生产，为基于蛋白质的药物提供了更好的微环境。热响应水凝胶是一种安全、有效、可注射的生物材料，用于封装和释放各种药物。我们已经建立了抗 VEGF 的 6 个月受控缓释和所提出的药物递送系统的优异生物相容性。该提案的总体目标是证明其功效。我们提出的体外和体内药物递送系统，并与传统疗法进行比较，假设在约 6 个月的较长时间内持续受控的抗 VEGF 释放将同样有效，甚至更有效。作为常规治疗的目标。具体目标 1 是定量比较所提出的药物递送系统与传统疗法在体外和体内模型中抑制血管生成反应的能力的功效和生物活性。具体目标 1 将分两部分完成： 1a 测试生物活性。体外模型中释放的抗 VEGF 药物的释放量，以及 1b 在激光诱导脉络膜新生血管 (CNV) 啮齿动物模型中比较了缓释抗 VEGF 药物与常规治疗的生物活性和治疗效果。具体目标 2 的目标是在体内模型中测量所提议的药物输送系统的长期疗效并监测潜在副作用（如果有）。将通过视网膜电图（ERG）监测长期疗效和潜在副作用。在对照组和治疗组中广泛使用临床反应、扫描激光检眼镜（SLO）血管成像血流测量、谱域光学相干断层扫描（SD-OCT）和组织学检查（终点）。抗 VEGF 需要一种实用且有效的眼后段递送方法。本提案中获得的知识将使该技术更接近临床实践。我们相信我们的药物递送系统将提供一种实用且有效的递送方法。提供抗病毒的有效方法该系统将通过减少注射频率并提供持续治疗的好处，对当前的医疗保健系统产生重大影响。