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载贝伐单抗白蛋白纳米粒对角膜新生血管的体内作用。

In vivo effect of bevacizumab-loaded albumin nanoparticles in the treatment of corneal neovascularization.

机构信息

Department of Chemistry and Pharmaceutical Technology, NANO-VAC Research Group, University of Navarra, Spain.

UNITEFA-CONICET, Department of Pharmacy, Faculty of Chemical Sciences (FCQ-UNC), National University of Córdoba, Argentina.

出版信息

Exp Eye Res. 2019 Aug;185:107697. doi: 10.1016/j.exer.2019.107697. Epub 2019 Jun 19.

DOI:10.1016/j.exer.2019.107697
PMID:31228461
Abstract

Corneal neovascularization (CNV) is associated with different ocular pathologies, including infectious keratitis, trachoma or corneal trauma. Pharmacological treatments based on the topical application of anti-VEGF therapies have been shown to be effective in the treatment and prevention of CNV. The aim of this work was to evaluate the effect of bevacizumab-loaded albumin nanoparticles in a rat model of CNV. Bevacizumab-loaded nanoparticles, either "naked" (B-NP) or coated with PEG 35,000 (B-NP-PEG), were administered once a day in the eyes of animals (10 μL, 4 mg/mL every 24 h) during 7 days. Bevacizumab and dexamethasone were employed as controls and administered at the same dose every 12 h. At the end of the study, the area of the eye affected by neovascularization was about 2-times lower for animals treated with B-NP than with free bevacizumab. In the study, dexamethasone did not demonstrate an inhibitory effect on CNV at the employed dose. All of these results were confirmed by histopathological analysis, which clearly showed that eyes treated with nanoparticles displayed lower levels of fibrosis, inflammation and edema. In summary, the encapsulation of bevacizumab in human serum albumin nanoparticles improved its efficacy in an animal model of CNV.

摘要

角膜新生血管(CNV)与多种眼部疾病有关,包括感染性角膜炎、沙眼或角膜创伤。基于抗血管内皮生长因子(VEGF)治疗的局部应用的药物治疗已被证明对 CNV 的治疗和预防有效。本工作旨在评估载贝伐单抗白蛋白纳米粒在 CNV 大鼠模型中的作用。贝伐单抗载纳米粒,无论是“裸”(B-NP)还是被聚乙二醇 35,000 修饰(B-NP-PEG),每天在动物眼睛中给药一次(10μL,4mg/mL 每 24h),持续 7 天。贝伐单抗和地塞米松被用作对照,以相同的剂量每 12h 给药一次。研究结束时,与游离贝伐单抗相比,用 B-NP 治疗的动物受新生血管化影响的眼睛面积降低了约 2 倍。在研究中,地塞米松在所用剂量下对 CNV 没有抑制作用。所有这些结果都通过组织病理学分析得到了证实,该分析清楚地表明,用纳米粒治疗的眼睛显示出较低水平的纤维化、炎症和水肿。总之,将贝伐单抗包封在人血清白蛋白纳米粒中提高了其在 CNV 动物模型中的疗效。

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