Butylphthalide nanoemulsion for management of dry age-related macular degeneration via antioxidant and anti-inflammatory mechanisms.

Dry age-related macular degeneration (dry AMD) is a posterior ocular segment disease characterized primarily by progressive retinal pigment epithelium degeneration, which is driven largely by oxidative stress. Effective treatment remains challenging owing to limited therapeutic agents and intrinsic physiological barriers that hinder drug delivery to the posterior eye. To address this, we developed a butylphthalide-loaded nanoemulsion (NBP-NE) that exhibits potent reactive oxygen species-scavenging and anti-inflammatory properties. Ex vivo permeation studies and pharmacokinetic analysis revealed that NBP-NE significantly enhances corneal and scleral penetration of butylphthalide (NBP), suggesting improved posterior ocular delivery. Moreover, NBP-NE exhibited robust antioxidant and anti-inflammatory effects in both in vitro and in vivo models, mechanisms associated with upregulation of the Nrf2 pathway and suppression of NF-κB signaling. In a sodium iodate-induced mouse model of dry AMD, topical administration of NBP-NE provided superior retinal morphological and functional protection by effectively attenuating oxidative stress and inflammatory responses. These findings represent the first reported application of NBP for dry AMD therapy and position NBP-NE as a promising noninvasive strategy for managing other oxidative stress-related posterior ocular diseases.