Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, China.
Institute of Biomedical Engineering, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, 270 Xueyuan Road, Wenzhou 325027, China.
J Control Release. 2022 Jul;347:449-459. doi: 10.1016/j.jconrel.2022.05.009. Epub 2022 May 19.
The unique physiological makeup of the eye limits the use of small-molecule drugs for treating the posterior segment of the eye. Nevertheless, transmembrane-peptide-mediated non-invasive drug delivery can serve as an ideal treatment strategy, as it is capable of delivering small-molecule drugs across the membrane in the form of eye drops, thereby achieving the effective treatment of neovascularisation in the posterior cavity. In this study, we screened and compared the posterior segment distribution of two poly(ethylene glycol)-distearoylphosphatidylethanolamine carriers modified using targeting-peptides. Thereafter, a transmembrane peptide (i.e., PENE) with a greater ability of transmembrane delivery was selected for delivering the anti-vascular drug (i.e., Axitinib) to the posterior segment of the eye. Using two different mouse models with fundus neovascular diseases, the complete non-invasive delivery of Axitinib to the posterior segment of the eye was confirmed using the targeted system; the designed eye drops (i.e., PENE-nanoparticles) could achieve drug distribution to the retina and veins of the eye as well as good drug permeability for renewal. Moreover, using the eye-drop treatment, neovascularisation was substantially reduced, demonstrating the high efficacy of this drug delivery system. This study, which combines nanodrug-loading technology and the transmembrane delivery of penetrating-peptides to achieve the goal of the non-invasive delivery of small-molecule drugs through the dense blood vessels of the sclera, shows wide applicability and considerably expands the use of ocular drugs. Thus, this study is expected to help develop a more acceptable drug administration strategy for the drug treatment of the posterior segment of the eye.
眼睛独特的生理结构限制了小分子药物用于治疗眼后段。然而，跨膜肽介导的非侵入性药物输送可以作为一种理想的治疗策略，因为它能够以眼药水的形式将小分子药物输送穿过细胞膜，从而实现对后腔新生血管的有效治疗。在这项研究中，我们筛选和比较了两种用靶向肽修饰的聚乙二醇-二硬脂酰基磷脂酰乙醇胺载体在后段的分布。然后，选择一种具有更强跨膜传递能力的跨膜肽（即 PENE）将抗血管生成药物（即阿昔替尼）递送至眼后段。使用两种具有眼底新生血管疾病的不同小鼠模型，通过靶向系统证实了阿昔替尼完全非侵入性地递送至眼后段；设计的眼药水（即 PENE-纳米颗粒）可以实现视网膜和眼部静脉的药物分布以及良好的药物通透性以实现更新。此外，通过滴眼治疗，新生血管显著减少，表明该药物递送系统具有很高的疗效。这项研究结合了纳米药物负载技术和穿透肽的跨膜传递，实现了通过巩膜密集血管非侵入性地递送小分子药物的目标，具有广泛的适用性，并极大地扩展了眼部药物的用途。因此，这项研究有望帮助开发出更能被接受的眼部药物治疗策略。
