This study aims to design chemically crosslinked thiolated cyclodextrin-based hydrogels and to evaluate their mucoadhesive properties via mucosal residence time studies on porcine small intestinal mucosa and on porcine buccal mucosa. Free thiol groups of heptakis(6-deoxy-6-thio)-β-cyclodextrin (β-CD-SH) were S-protected with 2-mercaptoethanesulfonic acid (MESNA) followed by crosslinking with citric acid. Cytotoxicity was assessed by hemolysis as well as resazurin assay. Hydrogels were characterized by their rheological and mucoadhesive properties. Ritonavir was employed as model drug for release studies from these hydrogels. The structure of S-protected β-CD-SH was confirmed by IR and H NMR spectroscopy. Degree of thiolation was 390 ± 7 µmol/g. Hydrogels based on native β-CD showed hemolysis of 12.5 ± 2.5 % and 13.6 ± 2.7 % within 1 and 3 h, whereas hemolysis of just 3.5 ± 2.8 % and 3.9 ± 3.0 % was observed for the S-protected thiolated CD hydrogels, respectively. Both native and S-protected thiolated hydrogels showed minor cytotoxicity on Caco-2 cells. Rheological investigations of S-protected thiolated β-CD-based hydrogel (16.2 % m/v) showed an up to 13-fold increase in viscosity in contrast to the corresponding native β-CD-based hydrogel. Mucosal residence time studies showed that thiolated β-CD-based hydrogel is removed to a 16.6- and 2.4-fold lower extent from porcine small intestinal mucosa and porcine buccal mucosa in comparision to the native β-CD-based hydrogel, respectively. Furthermore, a sustained release of ritonavir from S-protected thiolated β-CD-based hydrogels was observed. Because of their comparatively high mucoadhesive and release-controlling properties, S-protected thiolated β-CD-based hydrogels might be promising systems for mucosal drug delivery.

中文翻译：

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粘膜粘附聚合物：S-保护的硫醇化环糊精基水凝胶的设计

本研究旨在设计化学交联的硫醇化环糊精基水凝胶，并通过对猪小肠粘膜和猪颊粘膜的粘膜停留时间研究来评估其粘膜粘附特性​​。七（6-脱氧-6-硫代）-β-环糊精（β-CD-SH）的游离硫醇基团用2-巯基乙磺酸（MESNA）进行S-保护，然后用柠檬酸交联。通过溶血以及刃天青测定评估细胞毒性。水凝胶的特征在于其流变学和粘膜粘附特性​​。利托那韦被用作模型药物，用于从这些水凝胶中进行释放研究。 S-保护的β-CD-SH的结构通过IR和H NMR光谱证实。硫醇化度为390 ± 7 µmol/g。基于天然 β-CD 的水凝胶在 1 小时和 3 小时内表现出 12.5 ± 2.5 % 和 13.6 ± 2.7 % 的溶血，而 S 保护的硫醇化 CD 水凝胶的溶血分别仅为 3.5 ± 2.8 % 和 3.9 ± 3.0 % 。天然和 S-保护的硫醇化水凝胶对 Caco-2 细胞均表现出轻微的细胞毒性。 S-保护的硫醇化 β-CD 水凝胶 (16.2% m/v) 的流变学研究显示，与相应的天然 β-CD 水凝胶相比，粘度增加了 13 倍。粘膜停留时间研究表明，与天然 β-CD 基水凝胶相比，硫醇化 β-CD 基水凝胶从猪小肠粘膜和猪颊粘膜中的去除程度分别低 16.6 倍和 2.4 倍。此外，观察到利托那韦从 S-保护的硫醇化 β-CD 水凝胶中持续释放。由于其相对较高的粘膜粘附和释放控制特性，S-保护的硫醇化 β-CD 水凝胶可能是有前途的粘膜药物递送系统。