用于眼部持续抗 VEGF 递药的微孔药物输送系统。
Microporous Drug Delivery System for Sustained Anti-VEGF Delivery to the Eye.
机构信息
Boston Keratoprosthesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear and Schepens Eye Research Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
出版信息
Transl Vis Sci Technol. 2020 Jul 2;9(8):5. doi: 10.1167/tvst.9.8.5. eCollection 2020 Jul.
PURPOSE
To describe a novel microporous drug delivery system (DDS) for sustained anti- vascular endothelial growth factor (VEGF) delivery to the eye and to evaluate its efficacy in a corneal injury model.
METHODS
A macro-porous DDS (1.5 × 1.5 × 4 mm) loaded with 2 mg of bevacizumab was implanted subconjunctivally in three Dutch-belted pigmented rabbits after corneal alkali injury (2N NaOH). Three rabbits received sham DDS. Animals were followed for three months and assessed in vivo and ex vivo for corneal neovascularization (NV), epithelial defect, stromal scarring, endothelial cell loss, and expression of angiogenic and inflammatory markers in the cornea and retina.
RESULTS
Anti-VEGF DDS treatment led to complete inhibition of superior cornea NV and complete corneal re-epithelialization by day 58 whereas sham DDS resulted in severe cornea NV and persistent epithelial defect (9%∼12% of total cornea area) through the end of the study. Histologically, anti-VEGF DDS significantly reduced CD45 and F4/80 CD11b cell accumulation (79%, < 0.05) in the cornea, ameliorated tumor necrosis factor-α expression (90%, < 0.05), reduced corneal stromal scarring and prevented corneal endothelial cell loss, as compared to sham DDS. Moreover, anti-VEGF DDS achieved retinal penetration and reduction in retinal VEGF levels at 3 months.
CONCLUSIONS
Use of subconjunctival anti-VEGF DDS suppresses cornea NV, inflammation, stromal scarring, prevents endothelial cell loss, and abrogates retinal VEGF upregulation in a rabbit corneal alkali burn model. Moreover, it delivers anti-VEGF antibodies to the retina for three months. This delivery platform could enable antibody therapy of other corneal and retinal vascular pathologies.
TRANSLATIONAL RELEVANCE
We describe a method for sustained anti-VEGF delivery to the eye for the treatment of ocular injuries.
目的
描述一种新型的微孔药物递送系统（DDS），用于持续向眼部递送抗血管内皮生长因子（VEGF），并在角膜损伤模型中评估其疗效。
方法
在角膜碱烧伤（2N NaOH）后，将负载 2 毫克贝伐单抗的大孔 DDS（1.5×1.5×4mm）植入三只荷兰垂耳兔的结膜下。三只兔子接受假 DDS。动物被随访三个月，并在体内和体外评估角膜新生血管（NV）、上皮缺损、基质瘢痕、内皮细胞丢失以及角膜和视网膜中血管生成和炎症标志物的表达。
结果
抗 VEGF DDS 治疗导致 58 天时上角膜 NV 完全抑制，角膜完全再上皮化，而假 DDS 导致严重的角膜 NV 和持续的上皮缺损（占总角膜面积的 9%∼12%）直至研究结束。组织学上，抗 VEGF DDS 显著减少角膜中 CD45 和 F4/80 CD11b 细胞的积累（79%，<0.05），改善肿瘤坏死因子-α的表达（90%，<0.05），减轻角膜基质瘢痕形成，防止角膜内皮细胞丢失，与假 DDS 相比。此外，抗 VEGF DDS 在 3 个月时实现了视网膜穿透和降低视网膜 VEGF 水平。
结论
在兔角膜碱烧伤模型中，结膜下使用抗 VEGF DDS 可抑制角膜 NV、炎症、基质瘢痕形成、防止内皮细胞丢失，并消除视网膜 VEGF 的上调。此外，它可将抗 VEGF 抗体递送至视网膜长达三个月。这种递送平台可实现其他角膜和视网膜血管病变的抗体治疗。
翻译
刘金奇
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