Feasibility of corneal drug delivery of cysteamine using vitamin E modified silicone hydrogel contact lenses

Abstract

Cystinosis is an inherited genetic disease characterized by the accumulation of cystine crystals in several tissues including the cornea. The corneal manifestations of cystinosis are treated by hourly instillation of cysteamine eye drops each day while awake. The high frequency of eye drop instillation along with the long duration of treatment leads to poor compliance in many patients. We have combined in vitro experiments with mathematical modeling to investigate the feasibility of daily use of cysteamine loaded contact lenses to replace the hourly instillation of drops. Our approach was based on incorporation of vitamin E diffusion barriers into commercially available contact lenses to increase the duration of drug release. Contact lenses were first soaked in a solution of vitamin E in ethanol. Subsequently, the lenses were soaked in an aqueous solution of cysteamine to load the drug. The drug release profiles from vitamin E treated lenses were measured under sink conditions. In addition, drug oxidation rates were measured after exposing drug loaded contact lenses to humidified room air. To study further the feasibility of using contact lenses for the delivery of cysteamine, a mass transfer model was used to determine the rates at which the drug loaded in the lens is delivered to the cornea. The results show that vitamin E loading increases the release duration from 10min to about 3h in solution, thus allowing the possibility of extended drug delivery. In addition to improving the release profiles, vitamin E loading also improved the drug stability by reducing the oxidation rates. The mathematical modeling of drug transport in the eye suggested that the vitamin E loaded contact lens can provide the daily therapeutic dose without causing toxicity, while significantly increasing the bioavailability compared to eye drops. Based on the in vitro experimental results and the mathematical modeling, it is likely that a single contact lens worn for about 2h could achieve the same therapeutic effects as hourly instillation of eye drops.