As vascular endothelial growth factor in choroidal neovascularization is a major cause of visual loss of the elderlies and diabetics, gene therapy may offer an alternative treatment. However, siRNA instability and inefficient delivery are the main hindrances. To address this issue, we developed a nano-sized siRNA loaded therapeutic delivery system. The chitosan-hyaluronic acid nano-polyplexes were prepared by the modified ionic gelation method. The obtained nano-polyplex with a narrow size distribution, indicated no significant cytotoxicity in the MTT test and proper cellular uptake in confocal images. The RT-PCR analysis indicated remarkable gene silencing on HUVEC cells. The intravitreally administered nano-polyplexes in rabbits overcame both the vitreous and retina barriers and reached the posterior tissues efficiently. Intravitreal injections of the VEGFR-2 siRNA nano-polyplexes significantly reduced the size of the laser-induced choroidal neovascularization, compared to the control group. Consequently, the developed formulation can be a promising candidate for intravitreal delivery of siRNA.

中文翻译：

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用于玻璃体内VEGFR-2 siRNA递送的三甲基壳聚糖-透明质酸纳米复合物：配方和体内功效评估。

由于脉络膜新生血管中的血管内皮生长因子是老年人和糖尿病患者视力丧失的主要原因，因此基因治疗可能会提供另一种治疗方法。但是，siRNA的不稳定性和低效率的传递是主要障碍。为了解决这个问题，我们开发了纳米尺寸的siRNA载药治疗系统。采用改进的离子凝胶法制备了壳聚糖-透明质酸纳米复合物。获得的具有窄尺寸分布的纳米复合物，在MTT测试中没有显着的细胞毒性，并且在共聚焦图像中没有适当的细胞摄取。RT-PCR分析表明HUVEC细胞上显着的基因沉默。兔体内玻璃体内施用的纳米复合物克服了玻璃体和视网膜屏障，并有效地到达了后组织。与对照组相比，玻璃体内注射VEGFR-2 siRNA纳米复合物显着减小了激光诱导的脉络膜新血管形成的大小。因此，开发的制剂可以作为玻璃体内递送siRNA的有前途的候选者。