Cyclodextrin-Mediated Enhancement of Riboflavin Solubility and Corneal Permeability
Cyclodextrin-Mediated Enhancement of Riboflavin Solubility and Corneal Permeability
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DOI：
10.1021/mp3005963
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发表时间：
2013-02-01
影响因子：
4.9
通讯作者：
Khutoryanskiy, Vitaliy V.
中科院分区：
文献类型：
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作者：
Morrison, Peter W. J.;Connon, Che J.;Khutoryanskiy, Vitaliy V.
环糊精是由六、七和八个α-（1，4）-连接的吡喃葡萄糖亚基组成的水溶性环状低聚糖。本研究报告了在滴眼剂配方中使用不同的环糊精来改善核黄素的水溶性和角膜渗透性。核黄素是一种难溶性药物，在去离子水中的溶解度高达0.08 mg mL（-1）。在圆锥角膜的治疗中，它被用作局部给予眼睛的药物，以介导UV诱导的角膜交联。β-环糊精的水溶液（10-30 mg mL（-1））可以将核黄素的溶解度提高至0.12-0.19 mg mL（-1），而较高浓度的α-环糊精（100 mg mL（-1））实现了0.11 mg mL（-1）的较低水平的提高。发现其他寡糖对于此目的是无效的。用新鲜和冷冻保存的牛角膜进行的体外扩散实验已经证明β-环糊精增强核黄素的渗透性。通过角膜的显微组织学分析研究了这种增强的机制，并在本文中进行了讨论。
Cyclodextrins are water-soluble cyclic oligosaccharides consisting of six, seven, and eight alpha-(1,4)-linked glucopyranose subunits. This study reports the use of different cyclodextrins in eye drop formulations to improve the aqueous solubility and corneal permeability of riboflavin. Riboflavin is a poorly soluble drug with a solubility up to 0.08 mg mL(-1) in deionized water. It is used as a drug topically administered to the eye to mediate UV-induced corneal cross-linking in the treatment of keratoconus. Aqueous solutions of beta-cyclodextrin (10-30 mg mL(-1)) can enhance the solubility of riboflavin up to 0.12-0.19 mg mL(-1), whereas the higher concentration of alpha-cyclodextrin (100 mg mL(-1)) achieved a lower level of enhancement of 0.11 mg mL(-1). The other oligosaccharides were found to be inefficient for this purpose. In vitro diffusion experiments performed with fresh and cryopreserved bovine cornea have demonstrated that beta-cyclodextrin enhances riboflavin permeability. The mechanism of this enhancement was examined through microscopic histological analysis of the cornea and is discussed in this paper.