Ophthalmic Econazole Hydrogels for the Treatment of Fungal Keratitis
Ophthalmic Econazole Hydrogels for the Treatment of Fungal Keratitis
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DOI：
10.1016/j.xphs.2017.12.028
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发表时间：
2018-05-01
影响因子：
3.8
通讯作者：
Fernandez-Ferreiro, Anxo
中科院分区：
文献类型：
--
作者：
Diaz-Tome, Victoria;Luaces-Rodriguez, Andrea;Fernandez-Ferreiro, Anxo
益康唑是治疗真菌性角膜炎的一种可行的替代疗法。然而，其低水溶性被认为是纳入眼科配方的主要限制。本研究采用环糊精对硝酸益康唑进行溶出，以达到最佳治疗浓度。相溶解度图表明α -环糊精是最有效的环糊精，随后通过1D、2D-NMR和分子模型在溶液中表征了α -环糊精形成的包合物。在天然多糖离子敏感水凝胶和透明质酸水凝胶两种类型的眼凝胶中均含有econazole - α -环糊精包合物。两种药物在鸡蛋试验和绒毛膜尿囊膜试验中均无眼部刺激，且随时间的推移，康康唑的释放受到控制。渗透性研究表明，与econazole- α -环糊精包合物溶液相比，水凝胶不会改变硝酸econazole通过牛角膜的渗透性。最后，使用正电子发射断层扫描进行的眼生物性能研究表明，这些水凝胶在眼睛上的滞留时间很长。结果表明，所研制的制剂具有很大的潜力，可作为益康唑眼部局部给药治疗真菌性角膜炎的载体。(C) 2018美国药剂师协会(R)。Elsevier Inc.出版。版权所有。
Econazole is a feasible alternative treatment in the management of fungal keratitis. Nevertheless, its low water solubility is considered the main limitation to the incorporation into ophthalmic formulations. In this work, econazole nitrate is solubilized by using cyclodextrins to achieve an optimum therapeutic concentration. Phase solubility diagrams suggest alpha-cyclodextrin as the most effective cyclodextrin and later the inclusion complex formed with this one was characterized in solution by 1D, 2D-NMR, and molecular modeling. Econazole-alpha-cyclodextrin inclusion complex was included in 2 types of ocular hydrogels: a natural polysaccharides ion-sensitive hydrogel and a hyaluronic acid hydrogel. Both of them show no ocular irritation in the hen's egg test on chorioallantoic membrane assay and a controlled econazole release over time. Permeability studies suggest that hydrogels do not modify the econazole nitrate permeability through bovine cornea in comparison with an econazole-alpha-cyclodextrin inclusion complex solution. Finally, ocular biopermanence studies performed using positron emission tomography show these hydrogels present a high retention time on the eye. Results suggest the developed formulations have a high potential as vehicles for the econazole topical ocular administration as fungal keratitis treatment. (C) 2018 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.