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

血管生成在肿瘤生长、转移和炎症等病理状态以及创伤修复等生理发育和过程中起着重要作用。在眼睛中，脉络膜新生血管（CNV）是年龄相关性黄斑变性（AMD）的主要并发症，在发达国家，AMD通常导致老年人严重的视力丧失。AMD的治疗方法有激光光凝、黄斑下手术和放射治疗等，但临床上尚未找到满意的治疗方法。另一方面，已经描述了几种抗血管生成剂如干扰素α、沙利度胺和TNP-470的作用。然而，这些药物的全身给药已被证明对AMD患者不产生真实的益处，因为这些药物不具有器官特异性亲和力并且它们的体内半衰期太短。药物的药物修饰导致优于使用游离药物的优点，这使得这些药物选择性地递送到靶组织导致使用较小剂量进行治疗方面的影响.我们已经证明了通过与水溶性聚合物的化学缀合，抗血管生成剂如TNP-470和干扰素β针对实验性CNV的被动靶向可能有益于治疗实验性CNV的功效。我们实验室最近的工作表明，单克隆抗体可能是一种有用的介质，用于活性药物靶向实验性CNV的内皮细胞。本研究的目的是通过药物的药物修饰来研究药物传递系统，并开发新的治疗人类眼部疾病的方法。

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.