Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, University of Innsbruck, 6020 Innsbruck, Austria; Department of Pharmaceutics, Faculty of Pharmacy, University of Sargodha, 40100 Sargodha, Pakistan.
Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, 54000 Lahore, Pakistan.
Int J Pharm. 2021 Apr 15;599:120451. doi: 10.1016/j.ijpharm.2021.120451. Epub 2021 Mar 4.
Thiolated β-cyclodextrin (β-CD) has the potential to enhance mucoadhesive and permeation enhancing properties on ocular mucosa. Thiolated β-CD was synthesized via replacement of all primary hydroxyl groups on β-CD backbone by halogen followed by substitution with thiol groups. The structure was confirmed by FT-IR and H NMR spectroscopy. Thiolated CD was characterized for hemolytic effect, ocular irritation, solubility enhancement, viscoelastic behavior and mucoadhesive properties. Moreover, the permeation enhancing effect of thiolated oligomer on different ocular tissues including conjunctiva, sclera and cornea was evaluated with sodium fluorescein (Na-Flu) as a marker. Thiolated β-CD displayed 5360 ± 412 µmol/g thiol groups. The newly synthesized oligomer did not show any hemolytic effect on red blood cells at a concentration of 0.5% (m/v) for an incubation period of 3 h and minimal corneal irritation effects without any inflammation within 72 h. Thiolated β-CD exhibited a 5.3-fold improved aqueous solubility as compared to the unmodified β-CD. Thiolated oligomer (0.5% m/v) enhanced the viscosity of mucus up to 6.2-fold within 4 h and provided a 26-fold prolonged ocular residence time due to mucoadhesion. Moreover, 0.5% (m/v) thiolated β-CD enhanced the permeation of Na-Flu 9.6-, 7.1- and 5.3-fold on conjunctiva, sclera and cornea, respectively. Based on these findings, thiolated β-CD might be a promising auxiliary agent for ocular drug delivery.
巯基化 β-环糊精（β-CD）有可能增强对眼部黏膜的黏附性和渗透增强特性。巯基化 β-CD 是通过用卤素取代 β-CD 主链上的所有伯羟基，然后用巯基取代来合成的。其结构通过傅里叶变换红外光谱（FT-IR）和核磁共振光谱（H NMR）进行了确认。对巯基化 CD 的溶血作用、眼部刺激性、溶解度增强、黏弹性和黏附性进行了表征。此外，还用荧光素钠（Na-Flu）作为标记物评估了不同眼部组织（包括结膜、巩膜和角膜）上的巯基化低聚物的渗透增强作用。巯基化 β-CD 显示 5360±412µmol/g 巯基。新合成的低聚物在 0.5%（m/v）浓度下孵育 3 小时，对红细胞没有任何溶血作用，在 72 小时内对角膜的刺激性最小，没有任何炎症。与未修饰的 β-CD 相比，巯基化 β-CD 的水溶解度提高了 5.3 倍。与未修饰的 β-CD 相比，巯基化低聚物（0.5% m/v）在 4 小时内将黏液的黏度提高了 6.2 倍，并通过黏附作用使眼部滞留时间延长了 26 倍。此外，0.5%（m/v）巯基化 β-CD 分别使 Na-Flu 在结膜、巩膜和角膜上的渗透增加了 9.6、7.1 和 5.3 倍。基于这些发现，巯基化 β-CD 可能是一种有前途的眼部药物传递辅助剂。
