Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Gakuen-cho 1, Fukuyama, Hiroshima 729-0292, Japan.
Int J Pharm. 2021 Dec 15;610:121061. doi: 10.1016/j.ijpharm.2021.121061. Epub 2021 Sep 1.
The present study focused on the development of an amphotericin B (AmB) nanoformulation for ophthalmic applications. Accordingly, AmB nanohydrogels (AHA/AmB) using alkyl glyceryl hyaluronic acid (Hyalorepair®, AHA), a hydrophobized hyaluronic acid, were prepared by employing the dialysis method, followed by assessments of physical properties, drug efficacy, and toxicity. In the AHA/AmB formulation, AmB existed in a self-aggregated and amorphous state in the hydrophobic environment of the AHA moiety. AHA/AmB was shown in vitro to interact with mucin, which is known to be expressed in the corneal epithelium and was expected to improve its corneal retention. Compared with the conventional AmB formulation, amphotericin B sodium deoxycholate, AHA/AmB had the same in vitro antifungal activity but significantly lower in vitro toxicity. These findings indicate that nanohydrogels prepared with AHA possess high fungal selectivity and serve as a promising system for ophthalmic AmB delivery.
本研究专注于开发一种用于眼部应用的两性霉素 B（AmB）纳米制剂。因此，通过使用透析法制备了两性霉素 B 纳米水凝胶（AHA/AmB），该纳米水凝胶使用了烷基甘油透明质酸（Hyalorepair®，AHA），这是一种疏水化的透明质酸，并对其物理性质、药效和毒性进行了评估。在 AHA/AmB 制剂中，AmB 在 AHA 部分的疏水环境中以自聚集和无定形状态存在。体外研究表明，AHA/AmB 与粘蛋白相互作用，粘蛋白已知在角膜上皮中表达，有望提高其在角膜中的滞留。与传统的 AmB 制剂两性霉素 B 去氧胆酸钠相比，AHA/AmB 具有相同的体外抗真菌活性，但体外毒性显著降低。这些发现表明，用 AHA 制备的纳米水凝胶具有很高的真菌选择性，是一种很有前途的眼部 AmB 递送系统。
