A Nanogel Formulation\nof Anti-VEGF Peptide for Ocular\nNeovascularization Treatment

Age-related macular degeneration (AMD) is an eye disorder\nthat\ncan lead to visual impairment in elder patients, and current treatments\ninclude repeated injections of monoclonal antibody-based antivascular\nendothelial growth factor (anti-VEGF) agents. This study investigates\nthe potential of a nanoformulation of a peptide anti-VEGF molecule\nfor neovascular AMD. Anti-VEGF peptide HRHTKQRHTALH (HRH), which has\nhigh affinity to VEGF-Fc receptor, was used as the bioactive agent\nto control neovascularization of the retina. The nanoformulation consisting\nof hyaluronic acid nanogel was generated by incorporating divinyl\nsulfone and cholesterol to increase the stability and control the\nsize of the nanodrug. The encapsulation efficacy of nanogel was 65%,\nand drug release was 34.72% at the end of 192 h. Obtained nanogels\nwere efficiently internalized in 15 min by human umbilical vascular\nendothelial cells (HUVECs) and ARPE-19 cells, and results indicate\nthat nanoformulation is not toxic to ARPE-19 cells, whereas it inhibits\nHUVEC proliferation owing to anti-VEGF peptide in the nanogel structure.\nIn the coculture experiment in which retinal penetration was modeled,\nit was observed that the nanogel reached HUVECs and negatively affected\ntheir proliferation without disturbing the monolayer of ARPE-19 cells. <i>In vivo</i> experiments with chick chorioallantoic membrane\nrevealed that nanogel formulation has higher antiangiogenesis activity\ncompared to free HRH. Additionally, in an oxygen-induced retinopathy\nmodel, the excessive growth of blood vessels was notably suppressed\nin mice treated with HRH-loaded nanogel. This research indicates that\nnanogels formulated in this study are promising candidates as a topical\ntreatment for AMD.