Glucocorticoids (e.g., dexamethasone (Dex)) are the mainstay in the treatment of non-infectious uveitis, but optimal drug delivery system to maximally realize its potent bioactivity is still lacking. In the present study, we rationally designed and screened a dexamethasone-peptide amphiphile (Dex-GGD), which instantly formed a prodrug supramolecular hydrogel in phosphate-buffered saline (PBS, pH = 7.4) without external stimuli for the topical ocular drug delivery. The obtained Dex-GGD hydrogel was thoroughly characterized by rheology, circular dichroism (CD), and transmission electron microscopy (TEM). The results showed that Dex-GGD exhibited a potent in vitro anti-inflammatory capacity in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages with minimal cytotoxicity against L-929 fibroblasts, ARPE-19 cells, and RAW 264.7 macrophages. In a rat model of experimental autoimmune uveitis (EAU), the severity of uveitis was significantly alleviated after the treatment with Dex-GGD hydrogel owing to its potent ability to reduce the influx of inflammatory cells from peripheral blood and suppress the activation of macroglia and microglia in the retina. In contrast to the treatment with an equivalent dose of dexamethasone sodium phosphate (Dexp), the intravitreal injection of Dex-GGD hydrogel hardly induced the apparent ocular side-effects (e.g., elevated intraocular pressure or fundus blood vessel tortuosity). As a result, the proposed Dex-GGD prodrug supramolecular hydrogel may be an effective and safe therapeutic option for improving the clinical management of uveitis.

糖皮质激素（例如地塞米松（Dex））是治疗非感染性葡萄膜炎的主要手段，但仍缺乏最佳的药物递送系统来最大程度地发挥其强大的生物活性。在本研究中，我们合理地设计和筛选了地塞米松-肽两亲物（Dex-GGD），其在磷酸盐缓冲液（PBS，pH = 7.4）中立即形成了前药超分子水凝胶，无需外部刺激即可进行局部眼部药物递送。通过流变学，圆二色性（CD）和透射电子显微镜（TEM）对获得的Dex-GGD水凝胶进行了彻底的表征。结果表明，Dex-GGD在体外表现出强效脂多糖（LPS）活化的RAW 264.7巨噬细胞具有抗炎能力，并且对L-929成纤维细胞，ARPE-19细胞和RAW 264.7巨噬细胞具有最小的细胞毒性。在实验性自身免疫性葡萄膜炎（EAU）的大鼠模型中，由于Dex-GGD水凝胶能够有效减少外周血中炎性细胞的流入并抑制巨胶质细胞和小胶质细胞的活化，因此可以显着缓解葡萄膜炎的严重程度。在视网膜上。与等剂量的地塞米松磷酸钠（Dexp）治疗相反，玻璃体内注射Dex-GGD水凝胶几乎不会引起明显的眼部副作用（例如，，眼内压升高或眼底血管弯曲。结果，提出的Dex-GGD前药超分子水凝胶可能是改善葡萄膜炎临床管理的有效和安全的治疗选择。