Although endophthalmitis is a serious sight-threatening disorder, combining anti-inflammatory agents and antibiotics has provided new methods for effectively controlling it. This paper reports that the co-assembly of a sparingly soluble antibiotic (levofloxacin; Lev) and dexamethasone-peptide amphiphile (Dex-SA-RGD) instantly generates a macroscopically supramolecular hydrogel (Lev/Dex-SA-RGD) without any external stimulus under physiological conditions, which could be used in synergistic therapy to cure endophthalmitis induced by Staphylococcus aureus (i.e., S. aureus). The resulting co-assembled supramolecular hydrogel was thoroughly characterized using rheology, circular dichroism, and transmission electron microscopy. An in vitro drug release study showed that Lev was rapidly released from the supramolecular hydrogel within 6 h, while Dex-SA-RGD escaped from the supramolecular hydrogel as a result of matrix erosion, and then acted as a prodrug to provide the sequentially slow release of active dexamethasone via the hydrolytic route. The Lev/Dex-SA-RGD supramolecular hydrogel showed high antibacterial activities against both gram-negative and gram-positive strains. Moreover, a rabbit endophthalmitis model induced by S. aureus showed that the intravitreal injection of the Lev/Dex-SA-RGD supramolecular hydrogel resulted in excellent therapeutic efficacy with no apparent damage or destruction of the retina, and dramatically suppressed inflammatory responses (e.g., leukocyte and lymphocyte infiltration, microglial activation, cytokine production, and retinal cell death). As a rational approach to investigate and apply the co-assembled hydrogel, this work presents the potential of synergistic intervention to prevent retinal tissue damage and vision impairment, and ultimately shows the clinical benefits of using supramolecular hydrogels for ocular drug delivery.

虽然眼内炎是一种严重的威胁视力的疾病，但抗炎药和抗生素的结合为有效控制它提供了新的方法。这篇论文报道了一种微溶性抗生素（左氧氟沙星；Lev）和地塞米松-肽两亲物（Dex-SA-RGD）的共组装，在没有任何外部刺激的情况下立即产生了宏观超分子水凝胶（Lev/Dex-SA-RGD）。生理条件下，这可能在协同治疗可用于治疗眼内炎诱导金黄色葡萄球菌（即，金黄色葡萄球菌）。使用流变学、圆二色性和透射电子显微镜对所得的共组装超分子水凝胶进行了彻底的表征。一种在体外药物释放研究表明，Lev 在 6 小时内从超分子水凝胶中快速释放，而 Dex-SA-RGD 由于基质侵蚀而从超分子水凝胶中逸出，然后作为前药提供活性地塞米松的顺序缓释通过水解途径。Lev/Dex-SA-RGD 超分子水凝胶对革兰氏阴性和革兰氏阳性菌株均显示出高抗菌活性。此外，由金黄色葡萄球菌诱导的兔眼内炎模型表明，玻璃体内注射 Lev/Dex-SA-RGD 超分子水凝胶可产生出色的治疗效果，没有明显的视网膜损伤或破坏，并显着抑制炎症反应（例如，白细胞和淋巴细胞浸润、小胶质细胞活化、细胞因子产生和视网膜细胞死亡）。作为研究和应用共组装水凝胶的合理方法，这项工作展示了协同干预预防视网膜组织损伤和视力障碍的潜力，并最终展示了使用超分子水凝胶进行眼部药物递送的临床益处。