Department of Ophthalmology, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
Theranostics. 2023 Jul 9;13(12):4030-4041. doi: 10.7150/thno.85627. eCollection 2023.
Orbital inflammation is a prevalent and prolonged ocular disease that poses a significant challenge to clinicians. Glucocorticoid Dexamethasone sodium phosphate (Dex) has demonstrated efficacy in the clinical treatment of nonspecific orbital inflammation. However, frequent administration is required due to the short half-life of Dex, which may lead to drug waste and adverse side effects. In this study, we co-assembled Dex with a weak acid responsive hydrogelator Py-Phe-Phe-Lys-Lys-OH (K) to obtain a novel supramolecular hydrogel Dex/K that could release Dex in a slow manner to treat orbital inflammation. The therapeutic effect of Gel Dex/K on orbital inflammation was verified by and experiments. experiments indicated that co-assembly of Dex with K significantly increased mechanic strength of the hydrogel, enabling a continuous release of 40% of total Dex within 7 days. experiments further demonstrated that sustained release of Dex from Gel Dex/K could effectively alleviate the infiltration of inflammatory cells and the release of inflammatory factors in the orbit of mice, improving symptoms such as increased intraocular pressure and proptosis. Additionally, Gel Dex/K mitigated the degree of tissue fibrosis and fatty infiltration by reducing the development of local inflammation in the orbit. Our research results indicate that Gel Dex/K could more efficiently achieve responsive drug release in orbit, providing an innovative method for treating orbital inflammation.
眼眶炎症是一种常见且持久的眼部疾病，给临床医生带来了巨大挑战。糖皮激素地塞米松磷酸钠（Dex）已被证明在非特异性眼眶炎症的临床治疗中有效。然而，由于 Dex 的半衰期较短，需要频繁给药，这可能导致药物浪费和不良反应。在这项研究中，我们将 Dex 与弱酸响应水凝胶剂 Py-Phe-Phe-Lys-Lys-OH（K）组装在一起，得到一种新型的超分子水凝胶 Dex/K，它可以缓慢释放 Dex 来治疗眼眶炎症。通过 和 实验验证了 Gel Dex/K 对眼眶炎症的治疗效果。 实验表明，Dex 与 K 的共组装显著增加了水凝胶的机械强度，使 40%的总 Dex 在 7 天内持续释放。 实验进一步表明，Gel Dex/K 中 Dex 的持续释放可以有效减轻小鼠眼眶中炎症细胞的浸润和炎症因子的释放，改善眼压升高和眼球突出等症状。此外，Gel Dex/K 通过减轻眼眶局部炎症的发展，减轻了组织纤维化和脂肪浸润的程度。我们的研究结果表明，Gel Dex/K 可以更有效地在眼眶中实现响应性药物释放，为治疗眼眶炎症提供了一种创新方法。
