Cysteamine eye drops are utilized for treating the ocular complications of cystinosis. While the eye-drop based therapy is effective, it suffers from potential problems related to drug stability and compliance. The cysteamine eye drop formulation (CystaranTM) is required to be kept frozen at temperatures < -15 oC and after thawing it has a maximum shelf life of a week, even under refrigerated conditions, due to oxidation into an inactive form. A more severe problem with the eye drops based cysteamine therapy is the potential for poor compliance due to the high frequency of eye drops needed to treat the disease effectively. We will address each of these limitations by developing a contact lens (Cystalens) that will be designed for sustained release of drug over 8 hours to mimic the current delivery but in a more patient friendly way. Since the drug cysteamine is prone to oxidation, we will design Cystalens to deliver a cysteamine prodrug, which will be hydrolyzed in the eye to release cysteamine. Contact lenses have been proposed in the past as optimal devices for drug delivery but, a crippling factor has been the difficulty in delivering drugs for an extended period without altering the properties of lenses. We solve this problem by an innovative approach of dispersing nanobarriers in contact lenses to allow extended release of drugs from the lenses, without impacting any critical property. We have already developed a vitamin E loaded contact lens for delivering cysteamine and conducted preliminary safety study in rabbits. These results are promising but drug oxidation remain an issue. This proposal is focused on designing contact lenses for sustained release of prodrugs and pharmacokinetic studies measuring drug concentrations in the eye to demonstrate the prodrug can be delivered and that the prodrug is hydrolyzed inside the eye to release cysteamine.
