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纳米颗粒介导的多激酶抑制治疗兔增殖性玻璃体视网膜病变

Multikinase inhibition-mediated proliferative vitreoretinopathy therapy by nanoparticles in rabbits.

作者信息

Arslan Elif, Ozturk Faruk, Uner Burcu, Tureli Serkan, Muftuoglu Sevda Fatma, Tas Cetin

机构信息

Department of Ophthalmology, Hacettepe University School of Medicine, Ankara, Turkey.

Department of Ophthalmology, Ulucanlar Eye Education and Research Hospital, Ankara, Turkey.

出版信息

Mol Vis. 2025 Mar 29;31:142-157. eCollection 2025.

Abstract

PURPOSE

To investigate the efficacy of nanoparticles in treating proliferative vitreoretinopathy (PVR) through clinical observation, histology, and immunohistochemistry, despite unsatisfactory surgical outcomes and failed therapies for the current PVR treatment.

DESIGN

Twelve rabbits were divided into control and nintedanib (NTB) groups. The rabbits underwent weekly ophthalmologic examinations over a period of four weeks.

METHODS

At the end of the fourth week, the rabbits' eyes were removed for histological and immunohistochemical evaluation. Three additional rabbits outside the PVR model were administered a 0.5% NTB-loaded liposomal formulation in one eye. The drug concentrations in the vitreous samples were determined using high-pressure liquid chromatography on days 1, 7, 14, and 35.

RESULTS

The PVR stages were low in the NTB group, and there was no significant difference between the NTB and control groups (p = 0.108). However, it is worth noting that the group treated with NTB had significantly fewer epiretinal membrane formations during the histological evaluation. In addition, the corrected fluorescence intensity measurement of the subjects for collagen-1 in the NTB group was significantly lower than that in the control group (p = 0.004). Most importantly, no significant adverse effects were observed.

CONCLUSIONS

Our study has provided preclinical support for a liposomal formulation containing NTB that, with single-dose administration, has the potential to be effective in vivo in preventing the development of PVR and its correlated pathologies without causing any significant side effects.

摘要

目的

尽管目前增殖性玻璃体视网膜病变(PVR)的手术效果不尽人意且治疗失败,但通过临床观察、组织学和免疫组化研究纳米颗粒治疗PVR的疗效。

设计

将12只兔子分为对照组和尼达尼布(NTB)组。兔子在四周内每周接受眼科检查。

方法

在第四周结束时,摘除兔子的眼睛进行组织学和免疫组化评估。在PVR模型外的另外三只兔子的一只眼睛中给予0.5%负载NTB的脂质体制剂。在第1、7、14和35天使用高压液相色谱法测定玻璃体样本中的药物浓度。

结果

NTB组的PVR分期较低,NTB组和对照组之间无显著差异(p = 0.108)。然而,值得注意的是,在组织学评估中,接受NTB治疗的组视网膜前膜形成明显较少。此外,NTB组中受试者胶原蛋白-1的校正荧光强度测量值明显低于对照组(p = 0.004)。最重要的是,未观察到明显的不良反应。

结论

我们的研究为含NTB的脂质体制剂提供了临床前支持,该制剂单剂量给药在体内有可能有效预防PVR及其相关病变的发展,且不会引起任何明显的副作用。

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