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作为三氯醋酸泼尼松龙载体的整体/水凝胶复合材料,通过抑制纤维蛋白溶解系统来治疗小鼠角膜新生血管。

Monolith/Hydrogel composites as triamcinolone acetonide carriers for curing corneal neovascularization in mice by inhibiting the fibrinolytic system.

机构信息

Medical College, Qingdao University, Qingdao, China.

State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, China.

出版信息

Drug Deliv. 2022 Dec;29(1):18-30. doi: 10.1080/10717544.2021.2014603.

Abstract

Corneal neovascularization is a serious corneal pathological change caused by various factors. The drug delivery system is of great significance for the effective treatment of corneal neovascularization. Herein, we developed and characterized a monolith/hydrogel composite as the triamcinolone acetonide (TA) carrier for curing corneal neovascularization. The composite was prepared by photo-initiated free radical polymerization of multi-methacrylate substituted dodecamine organic molecular cage and post-modified by the sequential photo-initiated free radical polymerization of acrylated gelatin. The globular morphology and structural property of as-prepared composites were evaluated by scanning electron microscopy, Fourier-transform infrared spectroscopy and solid-state cross polarization magic angle spinning carbon-13 nuclear magnetic resonance. Then swelling ratio and the TA loading capacity were investigated then. Compared with gelatin hydrogel, the composites exhibited a decreased swelling ratio and an improved loading capacity. With good biocompatibility, the composite can sustainedly release TA for up to 28 days, and effectively inhibit corneal neovascularization with an alkali burn-induced corneal neovascularization model. Additionally, tandem mass tags-labeled quantitative proteomics were performed to identify differentially expressed proteins between vascularized and devascularized corneas. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the inhibition process could be primarily linked to the fibrinolytic system. These results demonstrated the potential of monolith/hydrogel composites as delivery systems in the therapy for biomedical diseases.

摘要

角膜新生血管是由多种因素引起的严重角膜病变。药物传递系统对于有效治疗角膜新生血管具有重要意义。在此,我们开发并表征了一种整体/水凝胶复合材料作为曲安奈德(TA)载体用于治疗角膜新生血管。该复合材料通过多甲基丙烯酰基取代十二胺有机分子笼的光引发自由基聚合和随后的丙烯酰化明胶的顺序光引发自由基聚合进行制备。通过扫描电子显微镜、傅里叶变换红外光谱和固态交叉极化魔角旋转碳-13 核磁共振对所得复合材料的球形形态和结构性质进行了评估。然后研究了溶胀比和 TA 负载能力。与明胶水凝胶相比,复合材料表现出较低的溶胀比和提高的负载能力。该复合材料具有良好的生物相容性,可长达 28 天持续释放 TA,并有效抑制碱烧伤诱导的角膜新生血管模型中的角膜新生血管形成。此外,还进行了串联质量标签标记定量蛋白质组学以鉴定血管化和去血管化角膜之间的差异表达蛋白。京都基因与基因组百科全书富集分析表明,抑制过程主要与纤维蛋白溶解系统相关。这些结果表明整体/水凝胶复合材料作为生物医学疾病治疗中药物传递系统的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb8/8725936/f79ed905dc3c/IDRD_A_2014603_F0001_C.jpg

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