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

血管生成在肿瘤生长、转移、炎症等病理过程以及伤口修复等生理发育过程中发挥着重要作用。在眼睛中，脉络膜新生血管（CNV）是老年性黄斑变性（AMD）的主要并发症，在发达国家老年人中常常导致严重的视力丧失。激光光凝，黄斑下手术和放疗已被用于治疗黄斑变性。然而，临床上没有令人满意的治疗方法来修复视觉功能。另一方面，一些抗血管生成药物如干扰素，沙利度胺和TNP-470的作用已经被描述。然而，这些药物的全身给药已被证明对AMD患者没有真正的益处，因为这些药物不具有器官特异性亲和力，而且它们的体内半衰期太短。药物的药物修饰导致比使用游离药物的优势，这使得这些药物选择性地递送到目标组织，导致使用更小的剂量进行治疗，并导致减少不良副作用。我们已经证明，通过与水溶性聚合物的化学偶联，tnf -470和干扰素β等抗血管生成药物被动靶向实验性CNV的疗效可能有利于实验性CNV的治疗。此外，我们实验室最近的研究表明，单克隆抗体可能是实验性CNV中有效药物靶向内皮细胞的中介。我们的研究目的是通过药物的药物修饰来研究药物的传递系统，开发新的治疗人类眼病的方法。

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.