新生血管性黄斑变性等致盲性眼病目前主要的治疗策略是玻璃体腔内注射抗血管内皮生长因子（VEGF）等大分子蛋白类药物。然而长期治疗过程中反复的有创注射，感染和组织损伤等难以避免。因此，研发能突破眼生物学屏障、靶向眼底、无创的药物递送系统具有重要的现实意义。我们已通过噬菌体展示技术筛选出一新型眼部引导肽CC12，并对其穿膜作用和携带多肽类药物的效果作了论证。本项目将在前期研究的基础上，进一步探索CC12携带抗VEGF药物的穿膜特性和无创滴眼治疗新生血管性眼底病变的潜能。通过人视网膜色素上皮细胞系摄取内化、流式细胞分析、离体眼组织表观渗透率和动物模型等体内外实验，揭示CC12介导蛋白类药物的跨膜能力、无创治疗的有效性及其眼内应用的安全性；并利用计算机流体力学方法模拟眼部药物递送过程，辅助给药方案设计。本研究预期的结果将为实现蛋白类药物的无创眼内递送提供科学依据，具有重要的理论和现实意义。

Intravitreal injection of biological drugs, such as the widely used anti-vascular endothelial growth factor (VEGF) therapeutics, provides a potent prevention and treatment modality for "wet" type of age-related macular degeneration. However, this is an invasive strategy that can be exacerbated with repeated injections during the long-term therapy. Therefore, it is of great practical significance to develop a novel noninvasive drug delivery system that can penetrate the ocular biological barrier and target the retina. In our previous study, in vivo-directed evolution phage display technology was employed to identify a novel dodecapeptide, named CC12, with the ability to penetrate the ocular barrier in a noninvasive (via conjunctival sac instillation) manner. And data of multilevel evaluations demonstrate the penetration capacity of CC12. Based on that, this study will further explore the potential of CC12 carrying anti-VEGF drugs as eye drops to mediate noninvasive delivery in the treatment of neovascular fundus diseases. Experiments such as ARPE-19 cellular uptake, flow cytometry quantitative analysis, apparent permeability assay and animal models will be conducted to elucidate its ability of penetration, effectiveness of noninvasive intraocular delivery and safety of intraocular application. Meanwhile, intraocular drug delivery process will be simulated by computational fluid dynamics, which could help to determine the dosing regimen. This study will provide a practical way and a scientific method for enhancing the absorption of protein drugs by noninvasive intraocular drug delivery.