A biodegradable ophthalmic drug delivery device

一种可生物降解的眼科药物输送装置

基本信息

批准号：
7483310
负责人：
L. Raymond DeBarge
金额：
$ 10万
依托单位：
NOTUS LABORATORIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-01 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7483310
关键词：
Address Adrenal Cortex Hormones Adverse effects Age Age related macular degeneration Albumins Allergic rhinitis Animal Model Blindness Blood Vessels Breathing Budesonide Cell Line Chemistry Chronic Clinical Compatible Condition Cultured Cells Devices Diabetic Retinopathy Disease Dose Drug Combinations Drug Delivery Systems Drug Implants Ethylene Oxide Evaluation Eye Eye diseases Frequencies Future Gas Chromatography Generations Glucocorticoids Glycolic-Lactic Acid Polyester Goals Gold High Pressure Liquid Chromatography Human Implant In Vitro Inflammatory Injection of therapeutic agent Internet Investigation Laboratories Lung diseases Macular degeneration Marketing Mass Chromatography Medical Methodology Modeling Morbidity - disease rate Nasocort National Eye Institute Nose Numbers Oryctolagus cuniculus Outpatients Pharmaceutical Preparations Phase Phase I Clinical Trials Phosphate Buffer Photochemotherapy Physiological Polymers Population Porosity Positioning Attribute Posterior Uveitis Posterior eyeball segment structure Preparation Production Property Public Health Rate Research Residual state Running Safety Saline Sampling Scanning Electron Microscopy Screening procedure Severities Small Business Funding Mechanisms Small Business Innovation Research Grant Solutions Solvents Spectrum Analysis Standards of Weights and Measures Sterility Sterilization for infection control Structure Structure of retinal pigment epithelium Technology Tensile Strength Testing Therapeutic Therapeutic Agents Thick Titrations Triamcinolone Triamcinolone Acetonide United States National Institutes of Health Uveitis Vision Weight Western World Work absorption aging population base bevacizumab biodegradable polymer biomaterial compatibility cost cytotoxicity diabetic disorder of macula of retina experience glycolate implantable device implantation improved in vivo keratinocyte macular edema nanofiber nanoparticulate novel ophthalmic drug physical property polylactic acid-polyglycolic acid copolymer prospective scale up size

项目摘要

DESCRIPTION (provided by applicant): Our long-term research goal is to develop an ophthalmic, nanofiber-based, biodegradable device that will provide extended release of therapeutic agents to the posterior segment of the eye via transscleral and intravitreal approaches. This platform device will address the major technical problem in the treatment of posterior eye diseases (diabetic retinopathy, macular degeneration, and posterior uveitis), which is the need for repeated injections or long-term implantation of therapeutic agents with significant side effects. The specific aims of this Phase I project are to determine 1) which combinations and concentrations of poly(lactide-co-glycolide) (PLGA) with triamcinolone acetonide and budesonide produce a structurally stable nanofiber composite material under dry and wet conditions; 2) the in vitro rate of drug elution from samples; 3) the effect of ethylene oxide sterilization on the drug-nanofiber mat samples; and 4) the in vitro biocompatibility of samples with human ocular epidermal keratinocytes and retinal pigment epithelial cells. The results of Phase I will be used to carry promising nanofiber PLGA-ophthalmic drug combinations forward to Phase II laboratory in vivo studies with the ultimate goal of an efficacious, safe, and commercially successful treatment option for the aging population with posterior eye diseases. There is tremendous market potential for a nanofiber-based, biodegradable sustained release corticosteroid delivery platform. Diabetic macular edema (DME) is a primary cause of decreased vision in diabetic retinopathy, which is the number one cause of vision loss in the working age population in the U.S. and the western world. The estimated market potential for DME is estimated to be $1 Billion in the U.S. by 2013. Uveitis is a low frequency, high severity ocular disease which causes about 10% of blindness in the U.S. Posterior uveitis and macular edema are commonly treated with periocular and intravitreal injections. An intermediate-term (semi-annual), biodegradable corticosteroid implant with high potency and lower side effect profile is a very attractive alternative to repeated injections and available non-absorbed implanted devices. Corticosteroids are also being evaluated for treatment of wet macular degeneration (AMD) and vascular occlusive diseases. A prospective, multi-center National Eye Institute (NEI) trial is underway evaluating triple therapy using intravitreal triamcinolone and bevacizumab with photodynamic therapy for wet macular degeneration (VERTACL). PUBLIC HEALTH RELEVANCE: The exudative macular edema common to DME, uveitis, and AMD is a leading cause of blindness in the western world. The aim of this project is to develop a novel electrospun corticosteroid-laden, nanofiber-based drug delivery device. The successful completion of this project will reduce the morbidity and costs associated with ocular drug delivery, as well as improve vision loss in these common posterior segment diseases.

描述（由申请人提供）：我们的长期研究目标是开发一种基于纳米纤维的可生物降解的眼科装置，该装置将通过经巩膜和玻璃体内的方法向眼后段提供治疗药物的延长释放。该平台设备将解决眼后部疾病（糖尿病视网膜病变、黄斑变性、后葡萄膜炎）治疗中需要重复注射或长期植入治疗剂且副作用显着的主要技术难题。该第一阶段项目的具体目标是确定 1) 聚丙交酯乙交酯 (PLGA) 与曲安奈德和布地奈德的组合和浓度在干燥和潮湿条件下可产生结构稳定的纳米纤维复合材料； 2) 样品中药物的体外洗脱率； 3）环氧乙烷灭菌对药物纳米纤维垫样品的影响； 4）样品与人眼表皮角质形成细胞和视网膜色素上皮细胞的体外生物相容性。第一阶段的结果将用于将有前途的纳米纤维 PLGA-眼科药物组合推进到第二阶段实验室体内研究，最终目标是为患有后眼病的老年人群提供有效、安全和商业上成功的治疗选择。基于纳米纤维的、可生物降解的缓释皮质类固醇递送平台具有巨大的市场潜力。糖尿病性黄斑水肿 (DME) 是糖尿病视网膜病变视力下降的主要原因，也是美国和西方世界工作年龄人口视力丧失的头号原因。预计到 2013 年，DME 在美国的市场潜力将达到 10 亿美元。葡萄膜炎是一种频率低、严重程度高的眼部疾病，在美国导致约 10% 的失明。后葡萄膜炎和黄斑水肿通常采用眼周和玻璃体内治疗注射。中期（半年一次）、可生物降解的皮质类固醇植入物具有高效力和较低的副作用，是重复注射和可用的非吸收植入装置的非常有吸引力的替代方案。皮质类固醇也正在评估用于治疗湿性黄斑变性（AMD）和血管闭塞性疾病。美国国家眼科研究所 (NEI) 正在进行一项前瞻性、多中心试验，评估使用玻璃体内注射曲安西龙和贝伐单抗联合光动力疗法治疗湿性黄斑变性 (VERTACL) 的三联疗法。公众健康相关性：DME、葡萄膜炎和 AMD 常见的渗出性黄斑水肿是西方世界失明的主要原因。该项目的目的是开发一种新型静电纺丝皮质类固醇负载、基于纳米纤维的药物输送装置。该项目的成功完成将降低与眼部药物输送相关的发病率和成本，并改善这些常见后段疾病的视力丧失。