Surgical Retina, Singapore National Eye Centre, Singapore, Singapore.
Duke-NUS Graduate Medical School, Singapore, Singapore.
Br J Ophthalmol. 2019 Oct;103(10):1356-1360. doi: 10.1136/bjophthalmol-2018-313462. Epub 2019 Apr 30.
Inhibitors of vascular endothelial growth factors are used to treat a myriad of retinal conditions, including exudative age-related macular degeneration (AMD), diabetic macular oedema (DME) and diabetic retinopathy. Although effective, long-term efficacy is limited by the need for frequent and invasive intravitreal injections. The quest for sustained action therapeutics that can be delivered to target tissue in the least invasive manner is an arduous endeavour that has ended in premature failure for several technologies in Phase II or III trials. Nevertheless, there have been promising preclinical studies, and more are on the horizon: port delivery systems for the treatment of exudative AMD have entered Phase III trials and a wide array of preclinical studies have demonstrated the potential for nanoparticles, such as liposomes, dendrimers and cell penetrating peptides to deliver therapeutics into the posterior segment via minimally invasive routes. In this review, we discuss the challenges posed by ocular barriers for drug penetration and present the recent advancements of the most pertinent drug delivery platforms with a focus on the treatment of exudative AMD and DME.
血管内皮生长因子抑制剂被用于治疗多种视网膜疾病，包括渗出性年龄相关性黄斑变性（AMD）、糖尿病性黄斑水肿（DME）和糖尿病性视网膜病变。尽管这些药物有效，但长期疗效受到频繁和侵入性玻璃体内注射的限制。因此，人们一直在努力寻找能够以最小侵入性方式递送至靶组织的持续作用治疗药物，但在 II 期或 III 期临床试验中，有几种技术都以失败告终。然而，已经有一些有前景的临床前研究，而且还有更多的研究正在进行中：用于治疗渗出性 AMD 的眼部输送系统已进入 III 期临床试验，大量临床前研究表明，纳米颗粒（如脂质体、树枝状聚合物和穿透肽）具有通过微创途径将治疗药物递送至后段的潜力。在这篇综述中，我们讨论了眼部屏障对药物渗透带来的挑战，并介绍了最近最相关的药物输送平台的进展，重点是治疗渗出性 AMD 和 DME。
