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Targeted drug delivery using water-soluble polymer in the treatment of choroidal neovascularization.

使用水溶性聚合物靶向给药治疗脉络膜新生血管。

基本信息

批准号：
10557154
负责人：
HONDA Yoshihito
金额：
$ 8.19万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

Angiogenesis plays an important role in pathological conditions such as tumor growth, metastasis and inflammation as well as in physiological development and processes such as wound repair. In the eye, choroidal neovascularization (CNV) is a major complication of age-related macular degeneration (AMD), which often causes severe visual loss among the elderly in developed countries. Laser photocoagulation, submacular surgery and radiation have been used for the treatment of AMD.However, no satisfactory therapy has been established clinically to repair visual function. On the other hand, the effects of several anti-angiogenic agents such as interferon alpha, thalidomide, and TNP-470 have been described. However, systemic administration of these drugs has been shown to produce no real benefit for patients with AMD, because these drugs do not have organ-specific affinity and their in vivo half-life is too short.The pharmaceutical modification of drugs results in advantages over the use of free drugs, which makes selective delivery of these drugs to the targeted tissue lead to the use of smaller doses for treatment and result in a reduction in undesirable side effects. We have already demonstrated the efficacy that passive targeting of the anti-angiogenic agents such as TNP-470 and interferon beta against experimental CNV through chemical conjugation with water-soluble polymer might be beneficial in the treatment of experimental CNV.Moreover, recent works in our laboratory have indicated that monoclonal antibodies might be useful as a mediator for active drug targeting to the endothelial cells in experimental CNV.The objective of our study is to investigate the drug delivery system by means of the pharmaceutical modification of drugs and to develop new therapeutic methods of human ocular diseases.

血管生成在肿瘤生长、转移和炎症等病理条件以及伤口修复等生理发育和过程中发挥重要作用。在眼部，脉络膜新生血管(CNV)是老年性黄斑变性(AMD)的主要并发症，在发达国家，AMD常导致老年人严重的视力丧失。激光光凝、黄斑下手术和放射治疗已被用于AMD的治疗，但临床上尚未建立令人满意的修复视功能的治疗方法。另一方面，几种抗血管生成药物如干扰素α、沙利度胺和TNP-470的作用已被描述。然而，这些药物的全身给药对AMD患者并没有真正的好处，因为这些药物没有器官特异性亲和力，而且它们在体内的半衰期太短。药物的药物修饰比使用游离药物具有优势，这使得这些药物选择性地输送到靶组织，导致使用较小的剂量进行治疗，从而减少了不良反应。我们已经证明了TNP-470和干扰素β等抗血管生成剂通过与水溶性聚合物化学偶联来对抗实验性CNV的有效性，在实验性CNV的治疗中可能是有益的。此外，我们实验室最近的工作表明，单抗可能作为主动药物靶向实验性CNV的介体。本研究的目的是通过药物修饰来研究药物给药系统，并开发新的治疗人类眼部疾病的方法。