From extraction to ocular delivery: An integrated approach using apigenin and apigenin 7-O-glucoside nanosuspensions to treat corneal neovascularization

Corneal neovascularization (CV) is a vision-threatening condition characterized by the pathological ingrowth of blood vessels. While corticosteroids and anti-VEGF agents are standard treatments, their prolonged use is associated with significant ocular side effects. This study aimed to develop and optimize nanosuspensions of Apigenin (APG) and Apigenin-7-O-glucoside (APG 7) to enhance their ocular bioavailability and evaluate their efficacy in the treatment of CV. APG and APG 7 were isolated from Petroselinum crispum . Nanosuspensions were formulated using an anti-solvent precipitation method, optimized via a 23 factorial design considering PVA concentration, Span 80 concentration, and homogenization speed. The physical properties, including particle size, PDI, and zeta potential, were characterized. In vivo efficacy was assessed over a 7-day treatment period in an alkali-burn induced rat CV model through clinical scoring, histopathology, and immunohistochemical analysis of VEGFA and IL-6 expression. The optimized APG nanosuspensions exhibited a mean particle size of ∼166.9 nm with high stability. In vivo studies demonstrated that 0.05% APG nanosuspension significantly inhibited corneal angiogenesis, reduced stromal edema, and downregulated VEGFA and IL-6 expression compared to the untreated injury group (p < 0.05). Conversely, APG 7 formulations failed to show significant therapeutic efficacy, likely due to limited corneal permeability attributed to the glycoside moiety. The 0.05% APG nanosuspension presents a promising, non-invasive therapeutic alternative for CV management, offering effective anti-angiogenic activity with improved ocular delivery characteristics. © 2026 Elsevier B.V.