Therapeutic nanocoating of ocular surface
Therapeutic nanocoating of ocular surface
复制标题
眼表治疗性纳米涂层
DOI：
10.1016/j.nantod.2021.101309
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发表时间：
2021-10-02
期刊：
影响因子：
17.4
通讯作者：
Fan, Xianqun
中科院分区：
文献类型：
--
作者：
Chen, Liangbo;Wu, Feng;Fan, Xianqun
局部给药对于治疗眼部疾病至关重要，但其存在药物利用率低、长期频繁给药、眼表损伤等显着缺陷，在很大程度上限制了治疗效果并影响生活质量。在这里，我们描述了通过简单地滴注仿生载药纳米粒子，在眼表面形成持久且具有保护性的治疗性纳米涂层。涂有经过工程改造以过度表达整合素-β1的皮脂细胞膜，会产生粘附性纳米颗粒，可以特异性结合眼上皮纤连蛋白上的精氨酸-甘氨酸-天冬氨酸序列。通过引入皮脂细胞膜和相关脂质，包被的纳米粒子可以补充脂质层并有利于泪膜的稳定性。滴注后，在离体人类和体内小鼠研究中，由锚定在眼表面的纳米颗粒组成的纳米涂层可保留长达 24 小时。这种方法的治疗价值在小鼠和兔子的干眼病模型中得到了证明。携带临床地塞米松的纳米涂层可有效改善角膜上皮恢复，降低角膜混浊和炎症细胞因子水平，并恢复泪液分泌。本研究展示了一种保护眼表并延长各种药物局部递送的替代方案，支持了治疗性纳米涂层治疗眼部疾病的潜力。 (c) 2021 Elsevier Ltd. 保留所有权利。
Topical drug delivery is critical for treating ocular diseases but suffers from significant defects including low drug availability, long-term frequent administration, and damage to ocular surface, which largely restrict treatment efficacy and influence quality of life. Here, we describe the formation of a durable and protective therapeutic nanocoating on ocular surface by simply instilling biomimetic drug-loaded nanoparticles. Coating with sebocyte membranes that are engineered to overexpress integrin-beta 1 generates adhesive na-noparticles that can specifically bind to Arg-Gly-Asp sequence on the fibronectin of ocular epithelium. By virtue of the introduction of sebocyte membranes and the associated lipids, coated nanoparticles can supplement the lipid layer and benefit the stability of tear film. After instillation, formed nanocoating consisting of anchored nanoparticles on ocular surface retains up to 24 h during ex vivo human and in vivo mouse studies. Therapeutic values of this approach are demonstrated in mouse and rabbit models of dry eye disease. Nanocoating carrying clinical dexamethasone effectively improves corneal epithelium recovery, decreases corneal opacity and inflammatory cytokine levels, and restores tear secretion. The present study demonstrates an alternative to protect ocular surface and extend topical delivery of various drugs, sup-porting the potential of therapeutic nanocoating to treat eye diseases. (c) 2021 Elsevier Ltd. All rights reserved.