Luaces-Rodríguez Andrea, Díaz-Tomé Victoria, González-Barcia Miguel, Silva-Rodríguez Jesús, Herranz Michel, Gil-Martínez María, Rodríguez-Ares María Teresa, García-Mazás Carla, Blanco-Mendez José, Lamas María Jesús, Otero-Espinar Francisco Javier, Fernández-Ferreiro Anxo
Department of Pharmacology, Pharmacy and Pharmaceutical Technology and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), Santiago de Compostela, Spain; Clinical Pharmacology Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
Department of Pharmacology, Pharmacy and Pharmaceutical Technology and Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), Santiago de Compostela, Spain.
Int J Pharm. 2017 Aug 7;528(1-2):714-722. doi: 10.1016/j.ijpharm.2017.06.060. Epub 2017 Jun 19.
Cystinosis is a rare autosomal recessive disorder in which cystine crystals accumulate within the lysosomes of various organs, including the cornea. Ocular treatment is based on the administration of cysteamine eye drops, requiring its instillation several times per day. We have introduced the cysteamine in two types of previously developed ocular hydrogels (ion sensitive hydrogel with the polymers gellan gum and kappa-carrageenan and another one composed of hyaluronic acid), aiming at increasing the ocular retention in order to extend the dosing interval. The biopermanence studies (direct measurements and PET/CT) show that these formulations present a high retention time on the ocular surface of rats. From the in vitro release study we determined that both hydrogels can control the release of cysteamine over time, showing a zero order kinetics during four hours. At the same time, these hydrogels could act as corneal absorption promoters, as they allow a higher permeation of cysteamine through bovine cornea compared to a solution. HET-CAM test and cytotoxicity assays show no irritation on the ocular surface. These results demonstrate that the developed formulations present a high potential as vehicles for the topical ocular administration of cysteamine.
胱氨酸病是一种罕见的常染色体隐性疾病，其中胱氨酸晶体在包括角膜在内的各种器官的溶酶体内积聚。眼部治疗基于半胱胺滴眼液的给药，需要每天滴注数次。我们已将半胱胺引入两种先前开发的眼用水凝胶中（一种是含有结冷胶和κ-卡拉胶聚合物的离子敏感水凝胶，另一种由透明质酸组成），目的是增加眼部滞留时间以延长给药间隔。生物持久性研究（直接测量和PET/CT）表明，这些制剂在大鼠眼表面具有较长的滞留时间。从体外释放研究中我们确定，两种水凝胶都可以随时间控制半胱胺的释放，在四小时内呈现零级动力学。同时，这些水凝胶可以作为角膜吸收促进剂，因为与溶液相比，它们能使半胱胺通过牛角膜的渗透率更高。HET-CAM试验和细胞毒性试验表明对眼表面无刺激。这些结果表明，所开发的制剂作为半胱胺局部眼部给药的载体具有很大潜力。
