摘要
Topical formulations, commonly applied for treatment of anterior eye diseases, require frequent administration due to rapid clearance from the ocular surface, typically through the lacrimal drainage system or through over-spillage onto the lids. We report on a mucoadhesive nanoparticle drug delivery system that may be used to prolong the precorneal residence time of encapsulated drugs. The nanoparticles were formed from self-assembly of block copolymers composed of poly（D, L-lactide） and Dextran. The enhanced mucoadhesion properties were achieved by surface functionalizing the nanoparticles with phenylboronic acid. The nanoparticles encapsulated up to 12 wt.% of Cyclosporine A （CycA） and sustained the release for up to five days at a clinically relevant dose, which led us to explore the therapeutic efficacy of the formulation with reduced administration frequency. By administering CycA-loaded nanoparticles to dry eye-induced mice once a week, inflammatory infiltrates were eliminated and the ocular surface completely recovered. The same once a week dosage of the nanoparticles also showed no signs of physical irritation or inflammatory responses in acute （1 week） and chronic （12 weeks） studies in healthy rabbit eyes. These findings indicate that the nanoparticles may significantly reduce the frequency of administration for effective treatment of anterior eye diseases without causing ocular irritation.
热门明确的表达，通常申请了前面的眼睛疾病的治疗，从眼睛的表面由于快速的清理要求经常的管理，典型地通过眼泪的排水系统或通过在漏上到盖上。我们在一个 mucoadhesive nanoparticle 药交货系统上报导可以被用来延长包含的药的 precorneal 住处时间。nanoparticles 被形成从创作的块共聚物自己组装 poly (d， l 减水乳酸) 并且葡聚糖。提高的 mucoadhesion 性质被表面 functionalizing 完成有 phenylboronic 酸的 nanoparticles。nanoparticles 包含了直到 Cyclosporine A (CycA ) 的 12 wt.% 并且在临床上相关的剂量支撑了版本多达五天，它导致了我们与减少的管理频率探索明确的表达的治疗学的功效。由管理装载 CycA 的 nanoparticles 每周一次弄干导致眼睛的老鼠，煽动性渗透被消除，眼睛的表面完全恢复了。每周一次， nanoparticles 的剂量也不显示出的一样物理激怒或煽动性的回答签到尖锐(1 个星期) 并且长期(12 个星期) 在健康兔子眼睛学习。这些调查结果显示没有引起眼睛的激怒， nanoparticles 可以显著地为前面的眼睛疾病的有效处理减少管理的频率。
