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 10 min to about 3 h 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.