Transscleral Drug Delivery for Retinal Disorders

经巩膜给药治疗视网膜疾病

基本信息

批准号：
7907709
负责人：
HENRY Francis EDELHAUSER
金额：
$ 140.11万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7907709
关键词：
Affect Arts Basic Science Clinical Research Collaborations Data Data Set Discipline Disease Drug Delivery Systems Drug Kinetics Drug Transport Endophthalmitis Engineering Experimental Animal Model Experimental Models Eye Eye Infections Eyedrops Fibrin Tissue Adhesive In Vitro Injection of therapeutic agent Institutes Interdisciplinary Study Measures Methods Modeling Molecular Weight Nebraska Neural Retina Ocular orbit Operative Surgical Procedures Ophthalmology Pennsylvania Pharmaceutical Preparations Pharmacodynamics Pharmacologic Substance Physiology Posterior eyeball segment structure Research Research Personnel Retina Retinal Detachment Retinal Diseases Route Science Techniques Technology Testing Theoretical model Toxic effect Universities analytical method drug distribution improved in vivo macromolecule nanoparticle novel pre-clinical preclinical study research study therapeutic effectiveness

项目摘要

DESCRIPTION (provided by applicant): The Ophthalmology Department at Emory University leads a multidisciplinary collaboration with the Georgia Institute of Technology, University of Nebraska, and University of Pennsylvania. This collaboration was formed to improve drug delivery to the posterior segment of the eye. Drug delivery to this target is a significant challenge in the treatment of retinal disorders. Methods for drug treatment of the globe include systemic administration, eye drops, and injection into the orbit. Drug dilution, ocular infection, endophthalmitis, and surgical damage such as retinal detachment can occur with these techniques. Given these drawbacks, we hypothesize that transscleral approaches are better for posterior segment drug delivery. We propose to develop novel transscleral drug delivery approaches that use nanoparticles, microneedles, fibrin sealant, ontophoresis, and electoporation. We will a) examine the physiology of transscleral drug transport, b) establish analytical methods to determine the distribution of low molecular weight drugs as well as macromolecules to the various regions of the posterior segment, and c) demonstrate delivery and therapeutic effectiveness in experimental animal models. The drugs to be tested are known to affect retinal diseases in basic science experiments, pre-clinical studies, or clinical studies. This project entails collaborative research among investigators from various disciplines including ophthalmology, engineering, and pharmaceutical sciences. Milestones: Theoretical models will be completed during the first year; these will be post-experimentally reassessed annually. Drug delivery systems are established in vitro already, and during the first year will produce data sets for model refinement and establish starting parameters for in vivo studies in the first and second years. Toxicity studies will be completed during the second and third years. Pharmacokinetic and pharmacodynamic data will be collected during the third through fifth years. In the fourth and fifth years efficacy data are obtained. By accomplishing these pre-clinical tests, we will discover and develop new routes for efficacious delivery of drugs to the eye. These delivery techniques should be safer and more effective than the state of the art. Ultimately, these results will guide us in enhancing drug treatments in ophthalmic practice.

描述（由申请人提供）：埃默里大学的眼科系领导与内布拉斯加州大学佐治亚理工学院和宾夕法尼亚大学的多学科合作。这种合作旨在改善眼睛后部的药物输送。向该靶标的药物输送是视网膜疾病治疗的重大挑战。全球药物治疗的方法包括全身给药，眼滴和注入轨道。这些技术可能会出现药物稀释，眼部感染，内咽炎和手术损伤，例如视网膜脱离。鉴于这些缺点，我们假设跨孢子方法更好地适用于后段药物的递送。我们建议开发使用纳米颗粒，微针，纤维蛋白密封剂，原子疗法和选择性的新型跨孢子药物递送方法。我们将a）检查跨症药物转运的生理，b）建立分析方法，以确定低分子量药物的分布以及大分子对后段的各个区域的分布，c）在实验性动物模型中证明了递送和治疗有效性。已知要测试的药物会影响基础科学实验，临床前研究或临床研究中的视网膜疾病。该项目需要在各个学科的研究人员之间进行合作研究，包括眼科，工程和药科学。里程碑：理论模型将在第一年完成；这些将每年在经验丰富的重新评估。药物输送系统已经在体外建立，在第一年将生成模型改进的数据集，并在第一年和第二年为体内研究建立起始参数。毒性研究将在第二年和第三年完成。在第三至第五年，将收集药代动力学和药效学数据。在第四和第五年，获得了疗效数据。通过完成这些临床前测试，我们将发现并开发新的途径，以有效地将药物输送到眼睛。这些交付技术应该比最新技术更安全，更有效。最终，这些结果将指导我们在眼科实践中增强药物治疗。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Suprachoroidal drug delivery to the back of the eye using hollow microneedles.

DOI：
10.1007/s11095-010-0271-y
发表时间：
2011-01
期刊：
PHARMACEUTICAL RESEARCH
影响因子：
3.7
作者：
Patel, Samirkumar R.;Lin, Angela S. P.;Edelhauser, Henry F.;Prausnitz, Mark R.
通讯作者：
Prausnitz, Mark R.

Formulation to target delivery to the ciliary body and choroid via the suprachoroidal space of the eye using microneedles.

DOI：
10.1016/j.ejpb.2015.05.020
发表时间：
2015-09
期刊：
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
影响因子：
0
作者：
Kim YC;Oh KH;Edelhauser HF;Prausnitz MR
通讯作者：
Prausnitz MR

Comparison of suprachoroidal drug delivery with subconjunctival and intravitreal routes using noninvasive fluorophotometry.

DOI：
10.1371/journal.pone.0048188
发表时间：
2012
期刊：
PloS one
影响因子：
3.7
作者：
Tyagi P;Kadam RS;Kompella UB
通讯作者：
Kompella UB

Suprachoroidal delivery in a rabbit ex vivo eye model: influence of drug properties, regional differences in delivery, and comparison with intravitreal and intracameral routes.

兔离体眼模型中的脉络膜上递送：药物特性的影响、递送的区域差异以及与玻璃体内和前房内途径的比较。

DOI：
发表时间：
2013
期刊：
Molecular vision
影响因子：
2.2
作者：
Kadam,RajendraS;Williams,Jason;Tyagi,Puneet;Edelhauser,HenryF;Kompella,UdayB
通讯作者：
Kompella,UdayB

In vivo high-frequency, contrast-enhanced ultrasonography of uveal melanoma in mice: imaging features and histopathologic correlations.

小鼠葡萄膜黑色素瘤体内高频对比增强超声检查：成像特征和组织病理学相关性。

DOI：
10.1167/iovs.10-6794
发表时间：
2011
期刊：
Investigative ophthalmology & visual science
影响因子：
4.4
作者：
Zhang,Qing;Yang,Hua;Kang,ShinJ;Wang,Yanggan;Wang,GeoffreyD;Coulthard,Tonya;Grossniklaus,HansE
通讯作者：
Grossniklaus,HansE