Oxidized Porous Silicon Particles As A Intraocular Drug Delivery System

Abstract

 

Purpose:

 

Antiproliferative drugs have been shown to have a modest effect in proliferative vitreoretinopathy (PVR) probably because of their short intraocular half-life. We evaluated the safety profile and ocular pharmacokinetics of a novel drug delivery system; oxidized porous silicon particles (pSiO2) loaded with daunorubicin (DNR) as a potential long acting intravitreal drug delivery agent to prevent PVR and retinal surface proliferation.

 

Methods:

 

DNR-loaded pSiO2 drug particles were added to a custom-designed chamber, which duplicated the turnover rate of rabbit eye fluid. The fluid effluent was sampled at designated time points up to 60 days, to measure DNR concentration to determine the drug release profile. Subsequently, 3mg of pSiO2 particles loaded with 124 micrograms of DNR by covalent attachment, was injected in rabbits eyes (volume 0.1 ml). The fellow eyes served as controls, and were injected with 5% dextrose. The eyes were monitored by slit lamp, indirect ophthalmoscopy, tonometry, and electroretinography (ERG) at 2 weeks and 3 months for signs of toxicity. The animals were sacrificed at the end of the experiments and histological data were obtained on the control and study eyes.

 

Results:

 

The in-vitro release assay showed nearly linear release of DNR from the pSiO2 particles, in which 2.5% of DNR was released during a 60-day incubation in the flow chamber. This suggested that release could be sustained longer than 60 days. During in vivo studies over 3 months of observation, no clinical toxicity was noted. Intraocular pressure (IOP) of study eyes was 18.36± 5 versus the control eyes of 18.12± 3.8 (p=0.88). The b amplitude of the dark-adapted ERG of the study eyes were 96.2± 30.5 and that of the control eyes 91.7± 29.2 (p=0.64). The histology revealed normal retinal structures as compared to the control eyes.

 

Conclusions:

 

Oxidized pSi particles loaded with efficacious doses are nontoxic to ocular tissues. Covalently loaded daunorubicin demonstrated a slow release and long-lasting property, which may be useful for intraocular sustained drug delivery for PVR, trauma and other retinal surface proliferative diseases.  

 

Keywords: drug toxicity/drug effects • electroretinography: non-clinical • pathology: experimental