A sustained release cysteamine microsphere/thermoresponsive gel eyedrop for corneal cystinosis improves drug stability.
A sustained release cysteamine microsphere/thermoresponsive gel eyedrop for corneal cystinosis improves drug stability.
复制标题
用于角膜胱氨酸病的缓释半胱胺微球/热敏凝胶滴眼剂可提高药物稳定性。
DOI：
10.1007/s13346-020-00890-6
复制
发表时间：
2021
影响因子：
5.4
通讯作者：
Fedorchak,MorganV
中科院分区：
文献类型：
--
作者：
Jimenez,Jorge;Washington,MichaelA;Resnick,JaydeL;Nischal,KenK;Fedorchak,MorganV
胱氨酸病是一种罕见的代谢性隐性遗传病，胱氨酸在解氨酶体内的蓄积可导致全身器官和组织的损害。在眼睛中，胱氨酸以角膜胱氨酸晶体的形式在角膜中积聚，严重影响视力。半胱胺滴眼液每天给药6~12次，1周内用药，治疗角膜半胱氨酸晶体。给药方案严格，稳定性差，不方便，增加了治疗负担。为了减少给药频率和提高稳定性，我们将半胱胺重新配制成一种新型的控释滴眼液。在这项工作中，我们表征和评价了一种局部给药系统，该系统由包裹在带有温度响应性凝胶载体的聚合物微球中的半胱胺组成。采用喷雾干燥法制备了半胱胺胶囊。对半胱胺的体外释放、稳定性、眼刺激性和角膜渗透性进行了评价。这些数据表明，与1周的半胱胺水滴眼液相比，半胱胺胶囊的稳定性提高到7周。从我们的系统中的一滴释放研究表明，半胱胺的释放持续了24小时，超过了半胱胺滴眼液的最小量(6滴)。与传统的半胱胺滴眼液相比，我们系统中的半胱胺的刺激性和渗透性也可以忽略不计。实施了体内研究，以支持易服性、耐受性和24小时的滞留。这些研究表明，我们的控释和递送系统可以从安全的、每天一次的凝胶滴眼液中提供稳定的半胱胺。
AbstractCystinosis is a rare, metabolic, recessive genetic disease in which the intralysosomal accumulation of cystine leads to system wide organ and tissue damage. In the eye, cystine accumulates in the cornea as corneal cystine crystals and severely impacts vision. Corneal cystine crystals are treated with cysteamine eyedrops when administrated 6 to 12 times day and used within 1 week. The strict dosing regimen and poor stability are inconvenient and add to the burden of therapy. To reduce the dosing frequency and improve the stability, we present reformulation of cysteamine into a novel controlled release eyedrop. In this work, we characterize and evaluate a topical drug delivery system comprised of encapsulated cysteamine in polymer microspheres with a thermoresponsive gel carrier. Spray-dried encapsulation of cysteamine was performed. In vitro cysteamine release, stability, and ocular irritation and corneal permeation were evaluated. The data suggest that encapsulated cysteamine improves the stability to 7 weeks when compared with 1-week aqueous cysteamine eyedrops. Release studies from one drop of our system show that cysteamine release was present for 24 h and above the minimum cysteamine eyedrop amount (6 drops). Cysteamine from our system also resulted in negligible irritation and enhanced permeation when compared with traditional cysteamine eyedrops. In vivo studies were implemented to support ease of administration, tolerability, and retention for 24 h. These studies suggest that our controlled release delivery system may provide stable cysteamine from a safe, once daily gel eyedrop.Graphical abstract