PDF(Pubmed)
Abstract：
Cystinosis is a low-prevalence lysosomal storage disease. The pathomechanism involves abnormal functioning of the cystinosine lysosomal cystine transporter (CTNS), causing intraliposomal accumulation of the amino acid cysteine disulfide, which crystallizes and deposits in several parts of the body. The most common ophthalmic complication of cystinosis is the deposition of \"gold dust\" cystine crystals on the cornea, which already occurs in infancy and leads to severe photosensitivity and dry eyes as it gradually progresses with age. In the specific treatment of cystinosis, preparations containing cysteamine (CYA) are used. The availability of commercialized eyedrops for the targeted treatment is scarce, and only Cystadrops® are commercially available with strong limitations. Thus, magistral CYA-containing compounded eyedrops (CYA-CED) could have a key role in patient care; however, a rationally designed comprehensive study on the commercialized and magistral products is still missing. This work aims to build up a comprehensive study about commercialized and magistral CYA eye drops, involving pharmacokinetic and physicochemical characterization (applying mucoadhesivity, rheology test, investigation of drug release, and parallel artificial membrane permeability assays), as well as ex vivo tests, well supported by statistical analysis.
摘要：
胱抑素病是一种低患病率的溶酶体贮积病。病理机制涉及到胱氨酸溶酶体胱氨酸转运蛋白（CTNS）的异常功能，导致氨基酸半胱氨酸二硫化物的脂质体内积累，结晶并沉积在身体的几个部位。胱氨酸病最常见的眼科并发症是角膜上沉积的“金尘”胱氨酸晶体，这已经发生在婴儿期，并导致严重的光敏和干眼，因为它逐渐随着年龄的增长。在胱氨酸病的具体治疗中，使用含有半胱胺（CYA）的制剂。用于靶向治疗的商业化滴眼液很少，并且只有Cystadrops®是市售的,具有很强的局限性。因此，含有CYA的复合滴眼液（CYA-CED）可能在患者护理中起关键作用；然而，对商业化和治安产品进行合理设计的全面研究仍然缺失。这项工作旨在建立对商业化和治安CYA滴眼液的全面研究，涉及药代动力学和物理化学表征(应用粘膜粘附性，流变试验,药物释放调查，和平行的人工膜通透性测定)，以及离体测试，有统计分析的支持。
