Akademik Veri Yönetim Sistemi
ACS APPLIED BIO MATERIALS, cilt.7, sa.9, ss.6001-6013, 2024 (ESCI)
Age-related macular degeneration (AMD) is an eye disorder that can lead to visual impairment in elder patients, and current treatments include repeated injections of monoclonal antibody-based antivascular endothelial growth factor (anti-VEGF) agents. This study investigates the potential of a nanoformulation of a peptide anti-VEGF molecule for neovascular AMD. Anti-VEGF peptide HRHTKQRHTALH (HRH), which has high affinity to VEGF-Fc receptor, was used as the bioactive agent to control neovascularization of the retina. The nanoformulation consisting of hyaluronic acid nanogel was generated by incorporating divinyl sulfone and cholesterol to increase the stability and control the size of the nanodrug. The encapsulation efficacy of nanogel was 65%, and drug release was 34.72% at the end of 192 h. Obtained nanogels were efficiently internalized in 15 min by human umbilical vascular endothelial cells (HUVECs) and ARPE-19 cells, and results indicate that nanoformulation is not toxic to ARPE-19 cells, whereas it inhibits HUVEC proliferation owing to anti-VEGF peptide in the nanogel structure. In the coculture experiment in which retinal penetration was modeled, it was observed that the nanogel reached HUVECs and negatively affected their proliferation without disturbing the monolayer of ARPE-19 cells. In vivo experiments with chick chorioallantoic membrane revealed that nanogel formulation has higher antiangiogenesis activity compared to free HRH. Additionally, in an oxygen-induced retinopathy model, the excessive growth of blood vessels was notably suppressed in mice treated with HRH-loaded nanogel. This research indicates that nanogels formulated in this study are promising candidates as a topical treatment for AMD.