Drug Delivery and Translational Research ( IF 5.7 ) Pub Date : 2022-06-17 , DOI: 10.1007/s13346-022-01190-x Yu Wu 1 , Lalitkumar K Vora 1 , Ryan F Donnelly 1 , Thakur Raghu Raj Singh 1
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The discovery of proteins that neutralise vascular endothelial growth factors, such as pegaptanib, ranibizumab and aflibercept, can inhibit the process of angiogenesis, thereby restoring eyesight in individuals with retinal vascular disorders. However, due to the posterior location and chronic nature of retinal diseases, a safe and effective intraocular protein delivery system is currently lacking. Thus, dissolving bilayer microneedles (MNs) with the potential to deliver proteins to the back of the eye in an efficient and minimally invasive manner were developed in this study. A model protein, ovalbumin (OVA), was incorporated into MNs fabricated from different polymers, including hyaluronic acid (HA), polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). Optimised PVA/PVP MNs were demonstrated to be robust enough to pierce porcine sclera with > 75% of the needle length penetrating the sclera and dissolving within 150 s. SDS-PAGE and OVA-specific ELISA revealed that the bioactivity of the model protein was maintained during the manufacture of MNs. In hen’s egg-chorioallantoic membrane test, MNs fabricated from all chosen polymers were classified as non-irritants. Furthermore, ex vivo permeation studies showed that optimised MNs could permeate 86.99 ± 7.37% of OVA through the sclera, twice that of the needle-free patch (42.16 ± 3.95%), highlighting the capability of MNs to circumvent physical barriers and promote protein delivery to the posterior segment of the eye. In this work, a novel, efficient and safe intraocular protein delivery system was successfully established.
Graphical abstract
中文翻译：
快速溶解的双层微针能够以微创和高效的方式将蛋白质输送到眼后段
中和血管内皮生长因子的蛋白质的发现，例如哌加他尼、雷珠单抗和阿柏西普，可以抑制血管生成过程，从而恢复视网膜血管疾病患者的视力。然而，由于视网膜疾病的后部位置和慢性性质，目前缺乏安全有效的眼内蛋白递送系统。因此，本研究开发了可溶解的双层微针（MN），能够以有效且微创的方式将蛋白质输送到眼睛后部。将模型蛋白卵清蛋白 (OVA) 纳入由不同聚合物制成的 MN 中，包括透明质酸 (HA)、聚乙烯醇 (PVA) 和聚乙烯吡咯烷酮 (PVP)。优化的 PVA/PVP MN 被证明足够坚固，可以刺穿猪巩膜，> 75% 的针长度穿透巩膜并在 150 秒内溶解。SDS-PAGE 和 OVA 特异性 ELISA 显示模型蛋白的生物活性在 MN 的制造过程中得以保持。在母鸡的蛋绒毛尿囊膜测试中，由所有选定的聚合物制成的 MN 被归类为无刺激性。此外，离体渗透研究表明，优化的 MN 可以通过巩膜渗透 86.99 ± 7.37% 的 OVA，是无针贴片 (42.16 ± 3.95%) 的两倍，凸显了 MN 绕过物理屏障和促进蛋白质递送的能力到眼睛的后段。本工作成功建立了一种新型、高效、安全的眼内蛋白递送系统。
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