Targeting drug-delivery nanoparticles to sites of inflammation

描述（由申请人提供）：本项目的目的是开发一种基于纳米颗粒的药物递送系统，用于治疗渗出型老年性黄斑变性（ARMD）。ARMD是生活在工业化世界的55岁以上个体失明的主要原因。它影响了美国约1000万人，全球多达3000万人。有两种形式的疾病，这两种疾病都会导致中央视力的丧失。大约85%的患者具有不太严重的干性形式，其产生逐渐但很少完全的视力丧失。剩下的15%有严重的湿性或渗出性形式，导致快速，致残失明。湿性ARMD的特征还在于脉络膜新生血管形成（CNV），即源自脉络膜毛细血管床的异常血管在黄斑下的生长。研究已经将慢性炎症与两种形式的ARMD联系起来。新型抗血管生成剂的出现使得ARMD的药物治疗成为可能，但仅用于疾病的湿形式。这些治疗受到药物必须直接注射到眼睛中的事实的严重限制。该手术具有显著的并发症风险，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的需要或降低其频率的疗法。我们建议开发的基于壳聚糖的纳米颗粒递送系统旨在满足这一需求。这个第一阶段项目的成功完成将产生一种原型纳米颗粒，可以静脉注射到眼睛中发炎的血管中，并在几周到几个月的时间内局部释放抗血管生成剂。

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.