Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan.
Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine, Faculty of Medicine, Taipei, Taiwan.
Int J Biol Macromol. 2021 Jun 1;180:365-374. doi: 10.1016/j.ijbiomac.2021.03.017. Epub 2021 Mar 4.
Post-operative endophthalmitis (POE) is one of the most dreadful complications after intraocular surgery. For cataract surgery patients, both commercially available topical 0.5% levofloxacin and 1% prednisolone acetate (PA) ophthalmic solution require at least 3 to 4 times application daily. In this study, we develop a dual drug delivery system composed of the thermosensitive chitosan/gelatin-based hydrogel containing PA and levofloxacin-loaded nanoparticles (LNPs). LNPs with negative surface charge show the monodisperse (polydispersity index 0.045), nanosize (154.7 nm) and sphere-like structure. The optimal concentration of LNPs and PA to corneal epithelial cells was 5 μg/mL and 50 μg/mL, respectively. The developed dual drug delivery system (PAgel-LNPs) could gel at 34 °C within 63 s. The osmolarity of PAgel-LNPs was 301.2 ± 1.5 mOsm/L. PAgel-LNPs showed a sustained-release profile for 7 days. Post-treatment of PAgel-LNPs in TNF-α-damaged corneal epithelial cells could decrease the inflammation (inflammatory genes (TNF-α, IL-6, MMP-3 andMMP-9) and IL-6 production) and cell death. In ex-vivo rabbit model of S. aureus keratitis, the anti-inflammation and anti-bacterial property have been demonstrated. These results suggest that thermosensitive PAgel-LNPs may have the potential to use for the prevention of POE.
术后眼内炎（POE）是眼内手术后最可怕的并发症之一。对于白内障手术患者，市售的 0.5%左氧氟沙星和 1%醋酸泼尼松龙（PA）滴眼液每天至少需要应用 3 至 4 次。在这项研究中，我们开发了一种由含有 PA 和载左氧氟沙星纳米粒（LNPs）的温敏壳聚糖/明胶基水凝胶组成的双药物递送系统。带负电荷的 LNPs 显示单分散性（多分散指数0.045）、纳米尺寸（154.7nm）和类球形结构。LNPs 和 PA 对角膜上皮细胞的最佳浓度分别为 5μg/mL 和 50μg/mL。所开发的双药物递送系统（PAgel-LNPs）可在 34°C 下在 63s 内凝胶。PAgel-LNPs 的渗透压为 301.2±1.5mOsm/L。PAgel-LNPs 表现出 7 天的持续释放特征。在 TNF-α损伤的角膜上皮细胞中，PAgel-LNPs 的处理可以减少炎症（炎症基因（TNF-α、IL-6、MMP-3 和 MMP-9）和 IL-6 的产生）和细胞死亡。在金黄色葡萄球菌角膜炎的离体兔模型中，已经证明了抗炎和抗菌特性。这些结果表明，温敏 PAgel-LNPs 可能具有用于预防 POE 的潜力。
