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Controlled Release of Dexamethasone From an Intravitreal Delivery System Using Porous Silicon DioxideControlled Release of Intravitreal Dexamethasone



The current study aims to evaluate a porous silicon-based drug delivery system meant for sustained delivery of dexamethasone (Dex) to the vitreous and retina.


Dexamethasone was grafted covalently into the pore walls of fully oxidized porous silicon particles (pSiO2-COO-Dex), which then was evaluated for the pharmacological effect of the payload on cultured ARPE19 cells before intravitreal injection. The Dex release profile was investigated in a custom designed dynamic dissolution chamber to mimic the turnover of vitreous fluid in rabbit eyes. Ocular safety, in vivo release, and pharmacodynamics were evaluated in rabbit eyes, and the human VEGF-induced rabbit retinal vascular permeability model.


Loading efficiency of Dex was 69 ± 9 μg per 1 mg of the pSiO2-COO-Dex particles. Dynamic in vitro release demonstrated a sustained mode when compared to free Dex, with the drug half-life extended by 5 times. The released Dex was unaltered and biologically active. In vivo drug release in rabbit eyes revealed a mode similar to the release seen in vitro, with a vitreous half-life of 11 days. At 2 and 4 weeks after a single intravitreal injection of pSiO2-COO-Dex particles (mean 2.71 ± 0.47 mg), intravitreal 500 ng of VEGF did not induce significant retinal vessel dilation or fluorescein leakage, while these events were observed in the eyes injected with empty pSiO2 particles or with free Dex. The retinal vessel score from fluorescein angiography for the control eyes was double the score for the eyes injected with pSiO2-COO-Dex. No adverse reaction was observed for the eyes injected with drug-loaded pSi particles during the course of the study.


The porous silicon-based Dex delivery system (pSiO2-COO-Dex) can be administered safely into vitreous without toxicity. Dex release from the porous silicon particles was sustained for 2 months and was effective against VEGF-induced retinal vessel reaction.

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