In vitro analysis of triamcinolone acetonide dissolution and diffusion in vitreous substitutes

Intravitreal drug delivery requires reliable in vitro models that replicate the structural, mechanical and diffusional properties of the native vitreous body. With the increasing number of patients affected by age-related eye diseases, the need for developing novel therapies is rising. In this study, the diffusion of triamcinolone acetonide was investigated in various hydrogel-based vitreous substitutes using a modified pharmacopeial dissolution test method (United States Pharmacopeia apparatus 7) equipped with 3d-printed gel baskets and dialysis membranes in order to find the most promising in vitro vitreous substitute. Diffusion kinetics and rheological stability were evaluated in comparison to porcine vitreous as the biological reference. One-component gels like those consisting of a single gelling agent (hyaluronic acid gels, hypromellose gels and polyacrylamide gels) failed to achieve both rheological similarity and physiologically relevant diffusion behavior. In contrast, two-component non-covalent hydrogels, particularly hyaluronic acid-agar formulations, exhibited markedly improved performance. The already rheologically optimized formulation consisting of 0.22 % hyaluronic acid and 0.09 % agar most closely matched the diffusion profile of triamcinolone acetonide in porcine vitreous, while supplementation of the acceptor medium with additional 0.22 % hyaluronic acid further enhanced rheological stability over the experimental period. These findings highlight this hydrogel as a promising in vitro vitreous substitute for preclinical diffusion studies, offering a reproducible and potentially physiologically more relevant platform for in vitro intravitreal drug testing.