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Development of drug delivery system for choroidal neo-vasculization(CNV) using biodegradable high molecular implant

利用可生物降解高分子植入物开发脉络膜新生血管（CNV）给药系统

基本信息

批准号：
15390528
负责人：
KIRYU Junichi
金额：
$ 8万
依托单位：
Kawasaki Medical School (2005)Kyoto University (2003-2004)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Treatment with interferon β(INFβ) for diseases caused by choroidal neovasuculization(CNV) such as age related macular degeneration (AMD) was previously investigated.However, eye drops and systemically administered drugs cannot deliver therapeutic drug concentrations into vitreoretinal tissue and they cause systemic side effects. We developed a drug delivery system for the biodegradable implant of INF(3 with specific effects on CNV that had no systemic side effects.We developed biodegradable gelatin microspheres to which glutaraldehyde was added through alkarine and acid processes. Then we added basic fibroblast growth factor (bFGF) to these microspheres. These microspheres we investigated into the subretinal space of CNV models. After that, we implanted the microsphere complex with INFβ into the vitreal space (vitreal IFNβ injection group) or the subretinal space (subretinal IFNβ injection group). We estimated the time course of CNV changes in each group by ophthalmoscopy and fluorescein angiography.In the control group (n=2), CNV appeared two weeks after implantation, and it continue grow until four to eight weeks after implantation. Then, the CNV diminished. The time courses of CNV growth in vitreal IFNβ injection group(n=2) and microsphere group (the group into which only gelatin microspheres were implanted in the subretinal space, n=2) were similar to that of the control group. However, in the subretinal IFNβ injection group(n=2), CNV did not diminish, and we found evidence of proliferative vitreous retinopathy(PVR).We created CNV models into which gelatin microspheres with bFGF were implanted in the subretinal space. Vitreal IFNβ injection group and microsphere group showed no signs of recovery. More study of the CNV is needed in the future.

干扰素β(β)治疗老年性黄斑变性等脉络膜新生血管疾病已有研究，但滴眼液和全身给药不能将治疗药物浓度输送到玻璃体视网膜组织，并且会引起全身副作用。我们开发了一种用于可生物降解的INF(3)植入物的药物释放系统，该系统对CNV具有特异性作用，且没有全身副作用。我们通过碱性和酸性过程在可生物降解的明胶微球中加入戊二醛。然后我们在这些微球中加入碱性成纤维细胞生长因子(BFGF)。这些微球我们研究进入视网膜下间隙的CNV模型。然后，将含有干扰素β的微球植入玻璃体腔(玻璃体干扰素β注射组)或视网膜下腔(视网膜下干扰素β注射组)。对照组(n=2)CNV在植入后2周出现，并持续生长至植入后4~8周。然后，CNV减少了。玻璃体注射干扰素β组(n=2)和微球组(仅将明胶微球植入视网膜下腔组，n=2)的新生血管生长时间与对照组相似。然而，在视网膜下注射干扰素β组(n=2)，新生血管并没有减少，我们发现有增殖性玻璃体视网膜病变的证据。玻璃体干扰素β注射组和微球组未见恢复迹象。未来还需要对CNV进行更多的研究。