Intraocular Properties of Silicon Photonic Crystals for Intravitreal Drug Delivery and Sensing

Abstract

Abstract: : Purpose: To explore the intraocular properties of silicon photonic crystals as a self–reporting slow releasing intravitreal drug delivery system. We hypothesized that drugs can be loaded into the micro pores of the photonic crystals and slowly released into the vitreous after injection. And we further hypothesized that release of the loaded drug will result in a light reflection spectrum change of the photonic crystal, which could provide a non–invasive way to monitor the drug releasing profile. Methods: Pulsed electrochemical etching of a silicon chip produced a multilayered porous nanostructure. The porous film was lifted off the silicon substrate, and it was either oxidized or hydrosilylated then broken into micron–sized particles of 10 to 45 micrometers by sonication. These crystals were suspended in 5% dextrose. 100 microlitters of the photonic crystal dextrose suspension was injected into rabbit eyes (approximately 30000 crystals), and the fellow eyes were injected with 5% dextrose as control. Oxidized and hydrosilylated photonic crystals were evaluated for toxicity and duration with ophthalmoscopy, electroretinography (ERG), and pathology. Results: Intravitreal injections of both oxidized and hydrosilylated photonic crystals revealed no clinical toxicity compared to the controls at the course of 4 months and 2 months. After injection, photonic crystals were either floating in the vitreous or sitting on surface of the retina with a characteristic chromic spectrum when viewed by indirect ophthalmoscopy. There was no evidence of inflammation or toxicity. Over time, the photonic crystals eroded, lost the specific light reflection spectrum, and disappeared. The intraocular residence time was longer than 2 months. The ERG and histopathology evaluations are under way. Conclusions: Silicon photonic crystals are non–toxic following intravitreal injection and demonstrate a long intraocular residence time in the range of months. These studies suggest that porous silicon crystals may be used for delivering drug into vitreous to achieve sustained release and that drug release may be monitored in a non–invasive way by use of their characteristic light reflection spectrum.

Keywords: retina • vitreous • pharmacology