A triamcinolone acetonide palmitate nanoemulsion eye drop delivered by iontophoresis for the management of posterior uveitis.

Uveitis is a leading cause of global vision loss. Local corticosteroid therapy, notably intravitreal or suprachoroidal triamcinolone injections, remains central to its clinical management. However, frequent intraocular injections and poor patient compliance substantially increase the risk of complications such as endophthalmitis. Although eye drops represent a more attractive noninvasive alternative, their efficacy in treating posterior segment diseases is severely limited by ocular defense mechanisms, resulting in extremely low bioavailability (<5%). To address these challenges, we propose a strategy combining prodrug modification with physical permeation enhancement. Triamcinolone acetonide was converted into an ester prodrug and formulated into a nanoemulsion using a reverse emulsification method. When coupled with iontophoresis, this system significantly improved drug delivery efficiency to the posterior segment of the eye. In a rabbit model of experimental autoimmune uveitis (EAU), a single administration of triamcinolone acetonide palmitate nanoemulsion (TAP-NE) sustained anti-inflammatory effects for up to 14 days. It significantly downregulated inflammatory cytokines including IL‑6 and IL‑17, and alleviated uveitis by suppressing the activation of retinal macroglia (GFAP) and microglia (IBA‑1). Furthermore, it maintained blood-retinal barrier (BRB) integrity, thereby preventing subsequent intraocular damage. Safety evaluations confirmed its favorable biocompatibility, with no detectable ocular irritation or tissue injury. The TAP-NE system combined with iontophoretic delivery developed in this study offers a novel strategy for addressing uveitis as well as other ocular conditions associated with inflammatory processes.