Intravitreal properties of porous silicon photonic crystals: a potential self-reporting intraocular drug-delivery vehicle

Abstract

Aim: To determine the suitability of porous silicon photonic crystals for intraocular drug-delivery.

Methods: A rugate structure was electrochemically etched into a highly doped p-type silicon substrate to create a porous silicon film that was subsequently removed and ultrasonically fractured into particles. To stabilise the particles in aqueous media, the silicon particles were modified by surface alkylation (using thermal hydrosilylation) or by thermal oxidation. Unmodified particles, hydrosilylated particles and oxidised particles were injected into rabbit vitreous. The stability and toxicity of each type of particle were studied by indirect ophthalmoscopy, biomicroscopy, tonometry, electroretinography (ERG) and histology.

Results: No toxicity was observed with any type of the particles during a period of >4 months. Surface alkylation led to dramatically increased intravitreal stability and slow degradation. The estimated vitreous half-life increased from 1 week (fresh particles) to 5 weeks (oxidised particles) and to 16 weeks (hydrosilylated particles).

Conclusion: The porous silicon photonic crystals showed good biocompatibility and may be used as an intraocular drug-delivery system. The intravitreal injectable porous silicon photonic crystals may be engineered to host a variety of therapeutics and achieve controlled drug release over long periods of time to treat chronic vitreoretinal diseases.

Figure 1

Cross-sectional scanning electron micrograph image of an intact porous Si film prior to removal from the bulk silicon substrate and fracture into microparticles. The pores are aligned along the <100> direction of the original silicon crystal.

Figure 2

(A) Fresh porous Si particles in a droplet of 5% dextrose solution. Particle clumping is observed due to the hydrophobic nature of the unmodified porous Si particles. (B) Oxidised particles in a droplet of 5% dextrose solution. These particles were observed to be more dispersed in solution, presumably because of the hydrophilic nature of the SiO₂ surface.

Figure 3

(A) Photograph taken under a surgical microscope immediately after intravitreal injection of fresh porous Si particles. Particles can be observed suspended in the centre of the vitreous. A few small air bubbles mixed with the porous silicon particles are present at the top of the vitreous cavity (arrow). (B) Fundus photograph taken 1 week after the injection, showing porous Si particles dispersed in the vitreous (arrows). (C) Fundus photograph taken 2 weeks after injection, indicating that most of the particles have disappeared, and those remaining are barely observable. (D) Light microscopic image shows normal retina and choroids with a slight artefact of retinal detachment (asterisk) (33×, H&E staining).

Figure 4

(A) Photograph taken under a surgical microscope immediately after intravitreal injection of hydrosilylated porous Si particles. Particles can be observed suspended in the centre of the vitreous. (B) Fundus photograph obtained 3 months after injection. The particles are dispersed in the vitreous, and many demonstrated a distinctive blue colour corresponding to partial degradation and dissolution. (C) Dissecting microscope image of a rabbit eye cup, with hydrosilylated porous Si particles (small arrows) distributed on a normal-looking retina. Photograph was obtained 4 months after injection. Two white areas (large arrows) evident in the image arise from reflections of the illumination source. (D) Scanning electron microscope image of the hydrosilylated porous Si particles sampled from a rabbit eye 4 months after intravitreal injection. The sharp edges and pitted surface of the particles indicate a very slow erosion process.

Figure 5

(A) Fundus photograph taken immediately after intravitreal injection of oxidised porous Si particles using a Volk Pan retinal 2.2 lens coupled to the Canon fundus camera lens for a wider view of the fundus. The white and purple rings were from the lens reflection. Particles can be observed suspended in the centre of the vitreous above the optic nerve. (B) Fundus photograph of a rabbit eye 2 weeks after intravitreal injection of oxidised porous Si particles. Many violet (small arrow) particles can be seen. The violet colour indicates that significant oxidation and dissolution of the particles have occurred. Some of the particles have lost their vivid reflectance completely and appear brown in colour (large arrow). (C) Fundus photograph of the same rabbit eye, 9 weeks after intravitreal injection of oxidised porous Si particles. Many of the particles have degraded, and only a few brownish particles are observed (arrows). The fundus appears normal. (D) Light microscopic photograph of the retina and choroid from a rabbit eye harvested 4 months after intravitreal injection of oxidised porous Si particles. Normal chorioretinal morphology and structures are observed (33×, H&E staining).

Figure 6

(A) Fundus photograph taken 3 days after intravitreal injection of type B oxidised porous Si particles. Whitish aggregates of the particles can be observed suspended in the centre of the vitreous above the optic nerve (arrow). (B) Fundus photograph of a rabbit eye 2 months after intravitreal injection. The particles are dispersed, with a yellowish appearance (arrows). (C) Fundus photograph of a rabbit eye 5 months after intravitreal injection. Many of the particles have degraded; however, some greyish particles are still observed in the very inferior vitreous (arrow). (D) Light-microscopic photograph of the retina and choroid from a rabbit eye harvested 8 months after intravitreal injection. Normal chorioretinal morphology and structures are observed except for the artificial retinal detachment (asterisk) (62.5×, H&E staining).