摘要
小分子干扰RNA(siRNA)是一种治疗眼表疾病的潜在药物。以前的研究是通过将siRNA直接注入角膜或结膜。在本研究中我们试图采用另一种方法,即通过含有cy3示踪的siRNA (cy3-siRNA)和不同阳离子络合药物的眼药水将siRNA传递到鼠角膜,并评价鼠单纯疱疹病毒性角膜炎(HSK)中siRNA靶向HSV-1 ICP4 基因(ICP4-siRNA)的作用。Cy3-siRNA与脂质体2000、EntransterTM(体内)或PEO-PPO-PEO聚合物以不同比例混合。将复合物局部施用至正常、EDTA刺激和BALB/c鼠眼的上皮刮痕角膜后分析传递疗效。角膜上皮细胞中的最大荧光产量表明0.75 mg/ml PEI和20 μM cy3-siRNA复合传递每天8次持续2天最有效。在鼠SHK中,siRNA+PEI 眼药水的应用减少了角膜上皮的损伤,降低了角膜组织中病毒VP16的表达。这些结果证实了以下想法:siRNA可被制成眼药水随载体有效传递至角膜,制成含有 ICP4-siRNA的眼药水可抑制鼠角膜中的HSV-1复制。
关键词: 角膜,眼药水,1型单纯疱疹病毒,受感染的细胞蛋白4,聚乙烯亚胺,siRNA。
Current Molecular Medicine
Title:A New Approach of Delivering siRNA to the Cornea and its Application for Inhibiting Herpes Simplex Keratitis
Volume: 14 Issue: 9
Author(s): Z. Li, F. Duan, L. Lin, Q. Huang and K. Wu
Affiliation:
关键词: 角膜,眼药水,1型单纯疱疹病毒,受感染的细胞蛋白4,聚乙烯亚胺,siRNA。
摘要: Small interfering RNA (siRNA) is a potential agent for the treatment of ocular surface diseases. Previous studies delivered siRNA by directly injecting siRNA into cornea or conjunctiva. In the present study we sought to explore an alternative approach to deliver siRNA into mouse cornea via eye drops that contains cy3-labeled siRNA (cy3-siRNA) and different cationic complexing agents and to evaluate the effects of siRNA targeting HSV-1 ICP4 gene (ICP4-siRNA) on mouse herpes simplex keratitis (HSK). Cy3-siRNA was mixed with Lipofectamine 2000, EntransterTM-in vivo, polyethyleneimine (PEI) or PEO-PPO-PEO polymers at different ratios. The efficacy of delivery was analyzed after topical application of the complexes to normal, EDTA treated, and epithelial scraped cornea of BALB/c mouse eyes. Compared to the other delivery agents and schedules, PEI at 0.75 mg/ml with 20 μM cy3-siRNA complex delivered eight times daily for two days was the most efficient as revealed by its production of the greatest fluorescence in cornea epithelial cells. In mouse HSK, the application of ICP4-siRNA+PEI eye drops reduced the damage to the corneal epithelia and decreased viral VP16 expression in the corneal tissue. These results proved the idea that siRNA can be formulated into eye drops with carriers for effective delivery into the cornea and that the formulated eye drops containing ICP4-siRNA can inhibit HSV-1 replication in the mouse corneas.
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Cite this article as:
Z. Li, F. Duan, L. Lin, Q. Huang and Wu K., A New Approach of Delivering siRNA to the Cornea and its Application for Inhibiting Herpes Simplex Keratitis, Current Molecular Medicine 2014; 14 (9) . https://dx.doi.org/10.2174/1566524014666141021145909
DOI https://dx.doi.org/10.2174/1566524014666141021145909 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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