综述
ENGLISH ABSTRACT
眼部抗VEGF药物缓释系统研究进展
杨宋阳
张明亮 [综述]
李筱荣 [综述]
作者及单位信息
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DOI: 10.3760/cma.j.cn115989-20200612-00424
Progress in controlled ocular anti-VEGF drug release delivery system
Yang Songyang
Zhang Mingliang
Li Xiaorong
Authors Info & Affiliations
Yang Songyang
Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China
Yang Songyang is now working at Department of Ophthalmology, Zhengzhou Second Hospital, Zhengzhou 450006, China
Zhang Mingliang
Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China
Li Xiaorong
Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, China
·
DOI: 10.3760/cma.j.cn115989-20200612-00424
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摘要

新生血管是多种眼底疾病的特征性表现,如糖尿病视网膜病变、视网膜静脉阻塞和新生血管性年龄相关性黄斑变性等。越来越多的证据表明,血管内皮生长因子(VEGF)在新生血管的形成中至关重要,抗VEGF药物是治疗新生血管性眼底疾病的一线用药,取得了显著的效果,但是存在药物半衰期短、需要长期给药才能维持有效浓度等缺点,增加了患者的经济负担和医疗风险,降低了依从性,因此寻找一种新的眼内药物递送方式具有重要的临床意义。参考糖尿病患者使用胰岛素泵逐渐释放药物的原理,眼部抗VEGF药物缓释系统可在一段时间内持续释放抗VEGF药物,显著减少患者的注射频率,提高患者的依从性。目前,眼部抗VEGF药物缓释系统研究仍不成熟,多种眼部抗VEGF药物缓释系统正在进行不同阶段的临床试验,根据设计原理的不同,可分为微型泵-眼外储存给药系统、可生物降解植入物和不可生物降解植入物3大类,每种类型均有自身的特点。本文就正在进行临床试验的抗VEGF药物缓释系统进行总结和分析。

新生血管;血管内皮生长因子;玻璃体腔注射;药物缓释系统
ABSTRACT

Neovascularization is the hallmark of many fundus diseases, including diabetic retinopathy, retinal vein occlusion and neovascular age-related macular degeneration.More and more evidence suggests that vascular endothelial growth factor (VEGF) plays a critical role in neovascularization.Anti-VEGF drugs are the first-line treatment for neovascular fundus diseases and have achieved significant results.However, there are drawbacks such as short drug half-lives and the need for long-term administration to maintain effective concentrations, which increases the economic burden and medical risk for patients and reduces compliance.Therefore, finding a new method for intraocular drug delivery is of great clinical importance.Based on the principle that diabetes patients use insulin pumps to gradually release drugs, the ocular anti-VEGF drug delivery system can continuously release anti-VEGF drugs over a period of time, significantly reducing the injection frequency and improving patient compliance.At present, the research on ocular anti-VEGF drug delivery systems is still immature, and various systems are in different stages of clinical trials.According to different design principles, they can be divided into three categories with their characteristics, micropump (extraocular storage delivery systems), biodegradable implants, and non-biodegradable implants.This article summarized and analyzed the controlled ocular anti-VEGF drug release delivery systems currently in clinical trials.

Neovascularization;Vascular endothelial growth factors;Intravitreal injections;Controlled release drug delivery system
Li Xiaorong, Email: nc.defudabe.umtgnoroaixil
引用本文

杨宋阳,张明亮,李筱荣. 眼部抗VEGF药物缓释系统研究进展[J]. 中华实验眼科杂志,2023,41(06):612-616.

DOI:10.3760/cma.j.cn115989-20200612-00424

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视网膜色素上皮(retinal pigment epithelium,RPE)细胞、血管内皮细胞等均可产生血管内皮生长因子(vascular endothelial growth factor,VEGF),VEGF的作用主要是增加现有血管的通透性和促进新生血管生成,过量表达的VEGF促使脂质和蛋白质等大分子从血管逃逸到视网膜,形成血管周围组织水肿,发生糖尿病性黄斑水肿(diabetic macular edema,DME);另一方面,新生血管性年龄相关性黄斑变性(neovascular age-related macular degeneration,nAMD)中过量的VEGF促进脉络膜新生血管(choroidal neovascularization,CNV)生成,CNV向上生长突破Bruch膜和RPE导致出血和水肿,最终形成纤维瘢痕破坏黄斑中心的感光细胞 [ 1 ]。VEGF家族包括VEGF-A、VEGF-B、VEGF-C、VEGF-D和胎盘生长因子(placental growth factor,PIGF),VEGF-A可以选择性剪切表达为165、121、145等多种异构体 [ 2 ]。VEGF通过与血管内皮生长因子受体(vascular endothelial growth factor receptor,VEGFR)结合发挥作用,受体有VEGFR1(Flt1)、VEGFR2(Flk1/Kdr)和VEGFR3(Flt4),VEGFR2是介导VEGFA功能的主要受体,促使静止的内皮细胞向血管生成表型转化。以上3种受体均属于酪氨酸激酶受体家族(receptor tyrosine kinases,RTK),具有相似的结构,细胞外结构域包含7个免疫球蛋白同源结构域。抗VEGF药物是治疗眼底新生血管性疾病的有效手段,目前有多种正在研发的眼部抗VEGF缓释系统。本文就正在进行临床试验的抗VEGF药物缓释系统进行总结和分析。
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备注信息
A
李筱荣,Email: nc.defudabe.umtgnoroaixil
B
所有作者均声明不存在利益冲突
C
国家自然科学基金项目 (81900894)
天津市自然科学基金青年项目 (18JCQNJC11300)
天津市滨海新区卫生健康委一般扶持项目 (2022BWKY011)
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