Ocular Drug Delivery Nanowafer with Enhanced Therapeutic Efficacy
Ocular Drug Delivery Nanowafer with Enhanced Therapeutic Efficacy
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DOI：
10.1021/nn506599f
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发表时间：
2015-02-01
期刊：
影响因子：
17.1
通讯作者：
Acharya，Ghanashyam
中科院分区：
文献类型：
--
作者：
Yuan，Xiaoyong;Marcano，Daniela C.;Acharya，Ghanashyam
目前，眼部损伤的治疗方法是局部滴眼疗法。由于眼表屏障，局部滴眼液必须在一天内多次使用，导致青光眼、白内障和患者依从性差等副作用。本文介绍了一种纳米晶片给药系统的开发，在该系统中，聚合物和药物协同工作，以获得增强的治疗效果，而不良免疫反应可以忽略不计。纳米晶片是一个小的透明圆盘，其中包含载药纳米储存库的阵列。药物从纳米晶片的缓慢释放增加了药物在眼表面的滞留时间，并随后被周围的眼组织吸收。在规定的药物释放期限结束时，纳米晶片将溶解并褪色。阿昔替尼纳米晶片在治疗小鼠眼部烧伤模型中的角膜新生血管(CNV)方面显示了活体疗效。激光扫描共聚焦成像和RT-PCR研究表明，与每天两次局部滴眼疗法相比，每天服用一次阿西替尼纳米晶片的治疗效果是前者的两倍。阿昔替尼纳米晶片无毒，不影响眼烧伤后角膜的创面愈合和上皮恢复。这些结果证实，即使在较低的给药频率下，从阿西替尼纳米晶片释放的药物在抑制CNV方面比局部滴眼治疗更有效。
Presently, eye injuries are treated by topical eye drop therapy. Because of the ocular surface barriers, topical eye drops must be applied several times in a day, causing side effects such as glaucoma, cataract, and poor patient compliance. This article presents the development of a nanowafer drug delivery system in which the polymer and the drug work synergistically to elicit an enhanced therapeutic efficacy with negligible adverse immune responses. The nanowafer is a small transparent circular disc that contains arrays of drug-loaded nanoreservoirs. The slow drug release from the nanowafer increases the drug residence time on the ocular surface and its subsequent absorption into the surrounding ocular tissue. At the end of the stipulated period of drug release, the nanowafer will dissolve and fade away. Thein vivoefficacy of the axitinib-loaded nanowafer was demonstrated in treating corneal neovascularization (CNV) in a murine ocular burn model. The laser scanning confocal imaging and RT-PCR study revealed that once a day administered axitinib nanowafer was therapeutically twice as effective, compared to axitinib delivered twice a day by topical eye drop therapy. The axitinib nanowafer is nontoxic and did not affect the wound healing and epithelial recovery of the ocular burn induced corneas. These results confirmed that drug release from the axitinib nanowafer is more effective in inhibiting CNV compared to the topical eye drop treatment even at a lower dosing frequency.