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Lingyun Cheng, Elizabeth Wu, William R. Freeman, Michael J. Sailor, Jennifer Andrew, Laura Conner, Alejandra Nieto; Degradation And The Routes Of Clearance Of Intravitreal Hydrosilylated Porous Silicon Particles. Invest. Ophthalmol. Vis. Sci. 2012;53(14):496.
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We have reported the degradation and intravitreal safety profiles of porous silicon particles as vehicles for ocular drug delivery. Though porous silicon can be degraded in vitreous without toxicity, the routes of clearence of the degradation product, monomeric silicic acid (Si(OH)4), from the eye environment is not yet understood.
Ten pigmented rabbits were used for this study. The right eye of each animal was intravitreally injected with 3mg of hydrosilylated (1-undecylenic acid) porous silicon particles in 100 µL of 5% dextrose. The particles had an average size of 33 by 46 µM. After the intravitreal injections, two rabbits were sacrificed at each of these time points: 1 week, 2 weeks, 3 weeks, 5 weeks, and 8 weeks. Before sacrifice 1 to 2 ml of blood was sampled and the enucleated eye globes were dissected individually into aqueous, vitreous, and retina for quantitation of dissolved Si (as orthosilicate) using ICP-OES (Inductively Coupled Plasma-Optical Emission Spectroscopy). Normal rabbit vitreous and retina were used as controls.
No excess Si was detected in the blood samples. The Si concentration in the vitreous and aqueous compartments gradually decreased over time and Si concentration was consistently higher in vitreous than that in aqueous. The peak concentration in the vitreous was 25.5±5µg/ml and 18.9±0.05µg/ml in aqueous, while the peak concentration in the retina was only 2.4±0.8µg/g which was similar to the Si concentration in normal control retina samples (1.9±0.4µg/g). Si concentration in the vitreous at the last time point was 10.5±1.7µg/ml which was not significantly different from Si concentration in the normal control vitreous (11.85±1.6µg/ml). The concentration-time profile suggested a sustained degradation.
The data suggest that the degraded porous silicon in vitreous was mainly cleared through aqueous outflow pathways.
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