Fang Guihua, Wang Qiuxiang, Yang Xuewen, Qian Yu, Zhang Guowei, Tang Bo
School of Pharmacy, Jiangsu Key Laboratory of Inflammation and Molecular Drug Targets, Nantong University, Nantong, Jiangsu Province 226001, China.
Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China.
Carbohydr Polym. 2022 Feb 1;277:118889. doi: 10.1016/j.carbpol.2021.118889. Epub 2021 Nov 14.
Anterior uveitis is a sight-threatening inflammation inside the eyes. Conventional eye drops for anti-inflammatory therapy need to be administered frequently owing to the rapid elimination and corneal barrier. To address these issues, polypseudorotaxane hydrogels were developed by mixing Soluplus micelles (99.4 nm) and cyclodextrins solution. The optimized hydrogels exhibited shear-thinning and sustained release properties. The hydrogels exhibited higher transcorneal permeability coefficient (P, 1.84 folds) than that of drug solutions. Moreover, animal study indicated that the hydrogels significantly increased the precorneal retention (AUC, 21.2 folds) and intraocular bioavailability of flurbiprofen (AUC, 17.8 folds) in comparison with drug solutions. Importantly, the hydrogels obviously boosted anti-inflammatory efficacy in rabbit model of endotoxin-induced uveitis at a reduced administration frequency. Additionally, the safety of hydrogels was confirmed by cytotoxicity and ocular irritation studies. In all, the present study demonstrates a friendly non-invasive strategy based on γ-CD-based polypseudorotaxane hydrogels for ocular drug delivery.
前葡萄膜炎是一种威胁视力的眼部炎症。由于药物快速消除和角膜屏障的存在，用于抗炎治疗的传统眼药水需要频繁给药。为了解决这些问题，通过混合Soluplus胶束（99.4纳米）和环糊精溶液制备了聚准轮烷水凝胶。优化后的水凝胶具有剪切变稀和缓释特性。与药物溶液相比，水凝胶表现出更高的角膜透过系数（P，为药物溶液的1.84倍）。此外，动物研究表明，与药物溶液相比，水凝胶显著提高了氟比洛芬的角膜前滞留量（AUC，为药物溶液的21.2倍）和眼内生物利用度（AUC，为药物溶液的17.8倍）。重要的是，在降低给药频率的情况下，水凝胶在脂多糖诱导的葡萄膜炎兔模型中明显提高了抗炎效果。此外，通过细胞毒性和眼刺激研究证实了水凝胶的安全性。总之，本研究展示了一种基于γ-环糊精的聚准轮烷水凝胶的友好非侵入性眼部给药策略。
