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: 7109581
• 负责人: HENRY Jerrold KAPLAN
• 金额: $ 34.27万
• 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 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7109581
• 关键词: aging; angiogenesis; birth; blindness; blood vessels; drug delivery systems; emotions; eye; inflammation; lasers; lead; macular degeneration; model; particle; person with disability; selectins; vision

DESCRIPTION (provided by applicant): The purpose of this project is to develop a nanoparticle-based drug delivery system for use in the treatment of the exudative form of aged-related macular degeneration (ARMD). ARMD is the leading cause of blindness for individuals over fifty-five years of age that live in the industrialized world. It affects 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 eighty-five percent of patients have the less severe dry form that produces gradual but rarely complete vision loss. The remaining fifteen percent have the severe wet, or exudative, form that causes rapid, disabling blindness. Wet ARMD is further characterized by choroidal neovascularization (CNV), a growth under the macula of abnormal blood vessels originating from the choroidal capillary bed. Research has linked chronic inflammation to both forms of ARMD. The advent of novel anti-angiogenic agents has enabled pharmaceutical treatment of ARMD but only for the wet form of the disease. These treatments are severely limited by the fact that the drug must be directly injected into the eye. This procedure carries a significant risk of complication and generates understandable issues of patient acceptability. Estimates predict that as many as one half of patients will discontinue treatment because of ocular injection. Thus, there is a clear need for a therapy that either bypasses the need for ocular injection or reduces its frequency. The chitosan-based nanoparticle delivery system we propose to develop intends to meet this need. Successful completion of this Phase I project will result in a prototype nanoparticle that can be injected intravenously and home to inflamed blood vessels in the eye and release an anti-angiogenic agent locally over a period of weeks to months.

描述（由申请人提供）：该项目的目的是开发一种基于纳米颗粒的药物输送系统，用于治疗渗出型老年性黄斑变性（ARMD）。ARMD是工业化国家55岁以上人群失明的主要原因。它影响了美国大约1000万人，全球多达3000万人。这种疾病有两种形式，都会导致中央视力丧失。大约85%的患者有不太严重的干燥形式，导致逐渐但很少完全的视力丧失。剩下的15%是严重的湿型或渗出型，会导致迅速致残的失明。湿性ARMD的进一步特征是脉络膜新生血管（CNV），一种源自脉络膜毛细血管床的异常血管在黄斑下生长。研究已经将慢性炎症与两种形式的ARMD联系起来。新型抗血管生成药物的出现使ARMD的药物治疗成为可能，但仅限于湿型疾病。由于药物必须直接注射到眼睛里，这些治疗方法受到了严重的限制。这种手术有很大的并发症风险，并产生患者可接受性的可理解问题。据估计，多达一半的患者将因眼部注射而停止治疗。因此，显然需要一种绕过眼部注射或减少其频率的治疗方法。我们拟开发的壳聚糖基纳米颗粒输送系统就是为了满足这一需求。第一阶段项目的成功完成将产生一种纳米颗粒原型，可以静脉注射到眼睛发炎的血管中，并在几周到几个月的时间内局部释放抗血管生成剂。