Department of Ophthalmology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 10, 63-Ro, Yeongdeungpo-Gu, Seoul, 07345, Republic of Korea.
Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA, 94303, USA.
Sci Rep. 2024 Sep 18;14(1):21806. doi: 10.1038/s41598-024-62026-x.
Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1β, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1β and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1β and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries.
治疗干眼症眼部炎症的局部滴眼方法常常面临效率低和药物输送持续时间短等限制。纳米纤维可克服治疗干眼症眼部炎症的局部滴眼药物作用持续时间短的局限性。已经有一些尝试来开发合适的纳米纤维；然而，还没有理想的解决方案。在这里，我们通过静电纺丝制备了负载醋酸地塞米松（DEX）的聚己内酯（PCL）纳米纤维，作为一种潜在的眼用药物输送平台，用于治疗角膜损伤。39 只（7 周龄雄性）SD 大鼠在角膜碱烧伤后分为四组治疗：阴性对照组（无治疗组）；地塞米松滴眼液（DEX 组）；PCL 纤维（PCL 组）；负载地塞米松的 PCL（PCL+DEX 组）。我们通过观察上皮伤口愈合效果、角膜混浊和新生血管化的程度来评估 PCL+DEX 的治疗效果。此外，通过免疫化学、western blot 分析和定量实时 RT-PCR（qRT-PCR）研究了各种炎症因子，包括 IL-1β。PCL+DEX 组的组织学炎症表现较 DEX 组明显缓解，PCL+DEX 组的角膜基质中 IL-1β和 MMP9 减少。碱性烧伤后第 1 天，PCL+DEX 组促炎标志物（包括 IL-1β和 IL-6）的定量表达明显低于 DEX 组。值得注意的是，PCL+DEX 治疗明显抑制了新生血管形成，并增强了 DEX 在眼内炎症急性期的抗炎作用。综上所述，这些发现表明 PCL+DEX 可能是一种有效的角膜烧伤药物输送方法。
