Background: Natamycin is the only topical ophthalmic antifungal drug approved by the Food and Drug Administration (FDA) of the United States, but has unsatisfactory factors such as high dosing frequency.Methods: We report the synthesis and preparation of self-assembled poly(ethylene glycol)-block-poly(glycidyl methacrylate) (PEG-b-PGMA) micelles. These nanoparticles exhibit sustained delivery of a hydrophobic natamycin by topical administration on eye due to the hydrolysable properties of PGMA segments of micelle. Hydrolysis of glycidyl groups within a physiologically relevant environment provides an additional driving force for drug release by generation of hydrophilic hydroxyl groups to 'push' the encapsulated hydrophobic drug away from the resultant hydrophilic domains and into surrounding environment.Results: In vitro and in vivo results revealed that the self-assembled micelles and the encapsulated natamycin were not cytotoxic and the released drug have strong antifungal ability to Candida albicans. Importantly, sustained natamycin release from micelles leads to the reduced administration frequency of natamycin from 8 times per day to 3 times per day in rabbits suffering from fungal keratitis (FK).Conclusion: This study demonstrates a facile method that can greatly reduce dosing frequency of natamycin administration and thus improve long-term patient compliance.

中文翻译：

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降低治疗真菌性角膜炎的给药频率：纳他霉素从胶束溶液中持续释放。

背景：纳他霉素是美国食品和药物管理局（FDA）批准的唯一眼用抗真菌药物，但其给药频率高等因素并不令人满意。方法：我们报道了自组装聚乙烯的合成和制备乙二醇）嵌段聚（甲基丙烯酸缩水甘油酯）（PEG-b-PGMA）胶束。这些纳米颗粒由于胶束的PGMA片段的可水解特性而通过在眼部局部施用而显示出疏水游霉素的持续递送。生理相关环境中缩水甘油基的水解通过产生亲水性羟基将胶囊化的疏水性药物``推''离合成的亲水性区域并进入周围环境，为药物释放提供了额外的驱动力。体外和体内结果表明，自组装的胶束和包封的游霉素没有细胞毒性，并且所释放的药物对白色念珠菌具有较强的抗真菌能力。重要的是，纳他霉素从胶束中的持续释放导致纳他霉素的给药频率从每天8次减少到每天3次，而这发生在真菌性角膜炎（FK）的兔子中。结论：本研究证明了一种简便的方法可以大大降低纳他霉素的给药频率那他霉素给药，从而改善了患者的长期依从性。