Department of Ophthalmology, Ningbo Eye Hospital, Ningbo, China.
Department of Science and Education, Ningbo Eye Hospital, Ningbo, China.
Curr Eye Res. 2022 Dec;47(12):1578-1589. doi: 10.1080/02713683.2022.2129071. Epub 2022 Oct 19.
To compare the therapeutic effects of different forms of nintedanib ophthalmic preparations on neovascularization corneal alkali burns in rats.
Forty rat models of left eye corneal alkali burns were constructed, and the five groups ( = 8) were treated with normal saline, dexamethasone ointment (dexamethasone), 0.2% nintedanib aqueous solution and nintedanib nano thermoreversible hydrogel (NNTH). A slit lamp microscope was used to observe the area of neovascularization. The levels of the inflammatory factors were detected by ELISA. HE staining was performed on the rat corneas. Vascular endothelial growth factor (VEGFA) was detected by immunohistochemistry, and the expression of corneal VEGFA and CD31 was detected by western blotting. An MTT assay was performed to detect the cytotoxicity of nintedanib on human corneal epithelial cells (HCECs) and human umbilical vein vascular endothelial cells (HUVECs). Cell migration was detected by a cell scratch assay, and the proportion of apoptotic cells was detected by Annexin/PI double staining. Immunofluorescence and western blotting were performed to detect the protein expression of VEGFA and CD31.
NNTH had a stronger inhibitory effect on corneal neovascularization (CNV) in alkali-burned rats while reducing the level of inflammatory factors. NNTH had a longer drug duration of release than nanoformulations in vitro. Nintedanib at low concentrations (<8 μM) had no significant cytotoxicity to HCECs but significantly induced apoptosis and inhibited the expression of VEGFA and CD31 and the migration of HUVECs.
Nanomorphic thermoreversible hydrogel is superior among the nintedanib ophthalmic preparations, showing better inhibition of CNV in alkali-burned eyeballs and it blocked the migration and proangiogenic ability of HUVECs.
比较不同形式的尼达尼布眼用制剂对大鼠角膜碱烧伤新生血管的治疗效果。
构建 40 只大鼠左眼角膜碱烧伤模型，分为 5 组（每组 8 只）：生理盐水组、地塞米松眼膏组、0.2%尼达尼布水溶液组和尼达尼布纳米温敏水凝胶（NNTH）组。使用裂隙灯显微镜观察新生血管面积。通过 ELISA 检测炎症因子水平。对大鼠角膜进行 HE 染色。通过免疫组化检测血管内皮生长因子（VEGFA），通过 Western blot 检测角膜 VEGFA 和 CD31 的表达。通过 MTT 法检测尼达尼布对人角膜上皮细胞（HCECs）和人脐静脉血管内皮细胞（HUVECs）的细胞毒性。通过细胞划痕实验检测细胞迁移，通过 Annexin/PI 双染法检测细胞凋亡比例。通过免疫荧光和 Western blot 检测 VEGFA 和 CD31 的蛋白表达。
NNTH 对碱烧伤大鼠角膜新生血管（CNV）的抑制作用更强，同时降低炎症因子水平。NNTH 在体外的药物释放持续时间长于纳米制剂。尼达尼布在低浓度（<8 μM）时对 HCECs 无明显细胞毒性，但能显著诱导细胞凋亡，抑制 VEGFA 和 CD31 的表达，并抑制 HUVECs 的迁移。
尼达尼布纳米温敏水凝胶制剂优于其他制剂，对碱烧伤眼球 CNV 有更好的抑制作用，能阻断 HUVECs 的迁移和促血管生成能力。
