The vitreous humor represents a significant barrier to the penetration of nanoparticulate-based ocular drug delivery systems. The gel structure and biochemical components of the vitreous will impact the rate of nanoparticle movement through the tissue to reach the retinal tissue. Also the structure of the vitreous, flow systems operating within it, age-related structural changes, and the presence of inflammation will also have a potential effect on movement. To effectively target the posterior retina, the physical properties of the nanoparticle formulation are a key element in the design of a system that will penetrate through the vitreous barrier.
Our results highlighted principal and consistent differences in small molecule composition and enzymatic activity of the vitreous depending on species. Interesting differences were demonstrated, showing that diet potentially can impact on components of and metabolites contained within the vitreous. Material will be exchanged between vascular and retinal tissue with the vitreous compartment and as a nonvascular, slowly equilibrating "sink" might reflect changes in transporter activity. As a first step, understanding the differences in the metabolic profile of vitreous from different species may impact interpretation of such activity across different species.
The results illustrate the ability of ToF-SIMS to characterize and provide spatial information about drug distribution within ocular tissues. Key differences in drug movement through the vitreous humor, toward both the anterior and the posterior tissues, in the living eye and the nonliving ovine eye were demonstrated, showing that dexamethasone sodium phosphate distribution through the vitreous is not determined by diffusion alone.
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