Evaluation of Corticosteroid–Loaded Silicone Microspheres for Controlled Intraocular Drug Delivery

Abstract

Abstract: : Purpose:To evaluate corticosteroid–loaded silicone microspheres as intraocular drug delivery system in combination with liquid endotamponades, in order to treat proliferative, neovascular or edematous retinal diseases. Methods:Drug loaded microspheres were produced from a two component silicone elastomer (Sylgard^®184/Dow Corning) starting from a chloroform in water dispersion with the solvent evaporation technique. The drug release of triamcinolone and dexamethasone was investigated using a pharmaceutical one compartment model. Results:Ideally spherical microspheres were obtained. The addition of 5–10% of the corticosteroids during preparation resulted in 4.2–9.4% drug content of the spheres. Drug release was monitored over a period of 3 months, which is appropriate for the treatment of proliferative vitreoretinopathy (PVR) or macular edema. During this period 46.7% of the total triamcinolone content were liberated. The release of dexamethasone at comparable initial drug content was significantly lower (<4%). The addition of NaCl during microsphere preparation resulted in an enhanced drug release (10.8% of total dexamethasone content). Drug level calculations indicated a dexamethasone concentration below the lower therapeutic concentration limit for the treatment of PVR. From the drug release data for triamcinolone and dexamethasone loaded silicone microspheres Higuchi kinetics were derived and diffusion coefficients of 4.9±0.4·10^–7 cm²/h to 1.4±0.1·10^–4 cm²/h were calculated. Conclusions: Based on drug level calculations, PVR may be effectively treated with triamcinolone loaded microspheres during temporary vitreous tamponade. Within the last years, intravitreal injection of triamcinolone has shown to have a positive effect on neovascular or edematous retinal diseases in non–vitrectomized eyes. Triamcinolone loaded microspheres may be combined with oily tamponades to reduce macular edema or retinal neovascularization due to severe diabetes or after macular rotation during the time of tamponade. Thereby systemic side effects can be minimized, a higher bioavailability and a long–term controlled release may be achieved.

Keywords: vitreous substitutes • proliferative vitreoretinopathy • pharmacology