Ocular Troxipide Nanosuspension Enhances Therapeutic Efficacy in an N-Acetylcysteine-Induced Dry Eye Model

Background/Objectives: Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability and decreased tear secretion, largely driven by chronic ocular surface inflammation. Although current therapies primarily target inflammation and tear film stabilization, their clinical efficacy is often limited by insufficient ocular surface retention. In this study, we explored a drug repositioning strategy for DED by developing a nanocrystalline formulation of troxipide (TRO), a gastric mucosal protective agent with cytoprotective properties. Methods and Results: A TRO nanosuspension (TRO-NPs) was successfully prepared by wet bead milling, yielding particles with a mean diameter of approximately 100 nm. Physicochemical characterization revealed that the crystalline structure, solubility, viscosity, pH, and osmolarity of the nanosuspension were comparable with those of the conventional TRO microsuspension (TRO-MPs). In contrast, the TRO-NPs exhibited markedly improved dispersion stability, maintaining particle suspension for at least 1 month after preparation. Repeated topical instillation of the TRO-NPs did not induce corneal toxicity or inflammation in rabbits, and resulted in significantly higher drug retention in the tear fluid than that observed for the TRO-MPs. Furthermore, in an N-acetylcysteine-induced rabbit dry eye model, repetitive instillation of the TRO-NPs significantly increased tear volume and mucin levels, leading to improved tear film stability. Conclusions: These findings demonstrate that nanosuspension-based formulations can enhance ocular surface retention and therapeutic efficacy of TRO. TRO-NPs therefore represent a promising nanomedicine-based repositioned therapy for the treatment of DED.