Targeting drug delivery nanoparticles to sites of inflammation

将药物输送纳米颗粒靶向炎症部位

• 批准号: 7684130
• 负责人: HENRY Jerrold KAPLAN
• 金额: $ 29.8万
• 依托单位: POTENTIA PHARMACEUTICALS, INC
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2009-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7684130
• 关键词: Acute; Address; Affect; Age; Age related macular degeneration; Age-Years; Aging; Amino Acids; Area; Binding; Biocompatible; Biodistribution; Blindness; Blood Vessels; Bypass; Cell Culture Techniques; Chronic; Complement; Complement Activation; Complement Inactivators; Complex; Conjunctival Hemorrhage; Cyclic Peptides; Data; Degenerative Disorder; Development; Diagnosis; Disease; Disorder by Site; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Encapsulated; Endophthalmitis; Endothelial Cells; Environmental Risk Factor; Exudative age-related macular degeneration; Eye; Eye diseases; FDA approved; Frequencies; Genetic; Glycolates; Goals; Home environment; Homing; In Vitro; Individual; Inflammation; Inflammatory; Injection of therapeutic agent; Lead; Legal Blindness; Life; Ligands; Link; Lymphocyte; Nonexudative age-related macular degeneration; Oryctolagus cuniculus; Pain; Pathogenesis; Patients; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Play; Process; Public Health; Research; Risk; Role; Selectins; Site; Small Business Technology Transfer Research; Staging; System; Therapeutic Agents; Time; Toxic effect; Toxicology; Vision; Work; base; density; in vivo; intravenous injection; meetings; nanoparticle; particle; programs; prototype; public health relevance; sialyl Lewis x; trafficking; vitreous floater

DESCRIPTION (provided by applicant): The purpose of this Phase II STTR project is to develop a nanoparticle-based drug delivery system for use in the treatment of dry age-related macular degeneration (AMD). AMD is the leading cause of blindness for individuals over fifty-five years of age that live in the industrialized world, affecting approximately 10 million people in the US and as many as 30 million worldwide. There are two forms of the disease, both of which cause a loss of central vision. Approximately fifteen percent have wet, or exudative, AMD, which causes rapid, disabling blindness. The remaining eighty-five percent of patients have dry AMD, a less severe form that produces gradual vision loss. At present, there are no approved pharmacological agents approved for the treatment of dry AMD. This project seeks study to develop a "smart" poly-lactic, glycolic acid (PLGA) nanoparticle drug delivery system that can home to sites of inflammation after intravenous injection. Homing is achieved through a mechanism similar to one used by lymphocytes recognize regions of inflammation. Once there, the particles will release a complement inhibitor over a sustained period time. A growing body of research links excessive complement activation with several diseases of aging, including AMD. The prototype nanoparticle developed in Phase I is able to selectively bind activated endothelial cells in cell culture. In vivo studies further show that the nanoparticles are able to bind inflamed blood vessels in the eye. In vitro studies showed that they are also able to release a complement inhibitor for periods in excess of 60 days. PUBLIC HEALTH RELEVANCE This application is critically concerned with developing a drug product that can be used to treat nonexudative age-related macular degeneration. There are currently no approved treatments for this disorder, making it a major the issue of public health. In the longer term, the goal of this work is to develop drug products that can selectively target and treat sites of disease action, particularly those associated inflammation and degenerative disease.

描述（由申请人提供）：该II期STTR项目的目的是开发一种基于纳米颗粒的药物输送系统，用于治疗干燥年龄相关的黄斑变性（AMD）。 AMD是居住在工业化世界的55岁以上个人失明的主要原因，影响了美国约1000万人，在全球范围内多达3000万。该疾病有两种形式，两者都会导致中央视力丧失。大约15％的AMD具有湿或渗出性的AMD，这会导致快速失明。其余85％的患者患有干燥AMD，这是一种不太严重的形式，会逐渐视力丧失。目前，尚无批准用于治疗干室的药理剂。该项目寻求研究以开发一种“智能”多乳酸，乙醇酸（PLGA）纳米粒子药物输送系统，该系统可以在静脉注射后回到炎症部位。通过类似于淋巴细胞识别炎症区域的机制来实现归巢。到达那里后，颗粒将在持续时间内释放补体抑制剂。越来越多的研究将过度补体激活与包括AMD在内的几种衰老疾病联系起来。在I期开发的原型纳米颗粒能够选择性地结合细胞培养中活化的内皮细胞。体内研究进一步表明，纳米颗粒能够结合眼睛中发炎的血管。体外研究表明，它们还可以释放超过60天的补体抑制剂。公共卫生相关性这一应用与开发可用于治疗与年龄相关的黄斑变性的药物产生关键有关。目前尚无对这种疾病的批准治疗方法，这使其成为公共卫生的主要问题。从长远来看，这项工作的目的是开发可以选择性靶向和治疗疾病作用部位的药物，尤其是那些相关的炎症和退化性疾病。