State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Int J Mol Sci. 2023 Mar 4;24(5):4957. doi: 10.3390/ijms24054957.
A novel drug delivery system designed for intraocular injection, gelatin methacryloyl (GelMA), has attracted much attention due to its sustained-release character and low cytotoxicity. We aimed to explore the sustained drug effect of GelMA hydrogels coupled with triamcinolone acetonide (TA) after injection into the vitreous cavity. The GelMA hydrogel formulations were characterized using scanning electron microscopy, swelling measurements, biodegradation, and release studies. The biological safety effect of GelMA on human retinal pigment epithelial cells and retinal conditions was verified by in vitro and in vivo experiments. The hydrogel exhibited a low swelling ratio, resistance to enzymatic degradation, and excellent biocompatibility. The swelling properties and in vitro biodegradation characteristics were related to the gel concentration. Rapid gel formation was observed after injection, and the in vitro release study confirmed that TA-hydrogels have slower and more prolonged release kinetics than TA suspensions. In vivo fundus imaging, optical coherence tomography measurements of retinal and choroid thickness, and immunohistochemistry did not reveal any apparent abnormalities of retinal or anterior chamber angle, and ERG indicated that the hydrogel had no impact on retinal function. The GelMA hydrogel implantable intraocular device exhibited an extended duration, in situ polymerization, and support cell viability, making it an attractive, safe, and well-controlled platform for treating the posterior segment diseases of the eye.
一种新型的眼内注射给药系统——明胶甲基丙烯酰(GelMA),由于其具有缓释特性和低细胞毒性而受到广泛关注。我们旨在探讨 TA 与 GelMA 水凝胶联合注射到玻璃体腔后药物的持续作用。通过扫描电子显微镜、溶胀测量、生物降解和释放研究对 GelMA 水凝胶配方进行了表征。通过体外和体内实验验证了 GelMA 对人视网膜色素上皮细胞和视网膜的生物安全性影响。水凝胶表现出低溶胀比、抗酶降解性和良好的生物相容性。溶胀性能和体外降解特性与凝胶浓度有关。注射后迅速形成凝胶,体外释放研究证实 TA-水凝胶的释放动力学比 TA 混悬液更慢、更持久。体内眼底成像、视网膜和脉络膜厚度的光学相干断层扫描测量以及免疫组织化学均未显示出视网膜或前房角的任何明显异常,ERG 表明水凝胶对视网膜功能没有影响。GelMA 可植入眼内水凝胶装置具有延长的持续时间、原位聚合和支持细胞活力的特点,是一种有吸引力的、安全的、可控的治疗眼部后节疾病的平台。