Neovascular retinal diseases, represented by wet age-related macular degeneration (wAMD), primarily affect critical ocular tissues such as the retina and choroid. The neovascularization at these sites is highly susceptible to leakage or rupture, leading to retinal edema or hemorrhage in the macular area. These conditions are major causes of vision impairment and blindness in the elderly. Due to multiple absorption barriers in the eye, the standard treatment for wAMD currently involves intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors, with aflibercept being the most commonly used. However, this invasive method requires high medical conditions and multiple injections, which can lead to complications such as vitreous hemorrhage, inflammation, and retinal detachment, resulting in poor patient compliance. If non-invasive ocular delivery of protein drugs could be achieved, patients would be able to self-administer treatment at home, significantly altering the current wAMD treatment paradigm and offering greater convenience and better therapeutic experience.
The research team led by Professor Gang Wei andProfessor Weiyue Lu from the School of Pharmacy at Fudan University extensively investigated the non-covalent interactions between a series of peptide delivery carriers and the protein drug aflibercept. Their findings revealed that these interactions were crucial for enhancing the intraocular absorption of aflibercept. Based on this principle, the team developed aflibercept/peptide non-covalent complex eye drops, which not only extend the retention time of aflibercept in the eye but also efficiently deliver it to the retina-choroid through the conjunctival-scleral pathway. The eye drops demonstrated therapeutic efficacy in a nonhuman primate wAMD model for the first time, showing comparable results to a single intravitreal injection of aflibercept. This study provides a safe and effective new treatment option for patients with various neovascular retinal diseases, including wAMD. The related results were published online in the internationally renowned journalAdvanced Science entitled "Peptide-bound Aflibercept Eye Drops for Treatment of Neovascular Age-related Macular Degeneration in Nonhuman Primates". The patent technology involved has been licensed to a biopharmaceutical company for the joint development of protein eye drop products with our college.
XingyanFan, the PhD candidate from the School of Pharmacy, Fudan University, is the first author. Professor Gang Wei is the corresponding author of this paper. The work was supported by grants from the National Natural Science Foundation of China and Shanghai Science and Technology Program.
For more information: https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202410744.
