Cysteamine-eluting contact lenses: integrating in vitro, in vivo, and in silico approaches for ocular drug delivery.

The objective of this study was to develop vitamin E nanobarrier contact lenses that can sustain the delivery of an equivalent amount of cysteamine to the cornea as eight drops per day regimen used in treating cystinosis. Senofilcon A lenses (14.0 mm diameter, -0.50 D power, 8.4 mm base curve) integrated with vitamin E and cysteamine were tested for drug release and fitted to the sink-release model to determine diffusivity and partition coefficient. The pharmacokinetics of cysteamine delivery by contact lenses and by control eye drops was measured in New Zealand white rabbits. Cysteamine delivery was modeled by a mechanistic model using contact lens parameters obtained from the in vitro studies along with known anatomical, physiological and drug specific parameters obtained from literature. The release duration of cysteamine increased from a few minutes in control lenses to about 2 and 6 h, in lenses loaded with 20 and 30 % vitamin E, respectively. In vivo studies showed that the contact lens-based approach can deliver significantly high concentrations compared to eye drops. The total mass of drug delivered by 20 % vitamin E loaded contact lens is more than six times the mass delivered by a single eye drop. The contact lens-based therapy achieves higher delivery than drops in the back of the eye tissues as well. The predictions of the mechanistic mathematical model are in good agreement with in vivo measurements for both eye drops and contact lenses. The contact lens-based delivery of cysteamine is a promising approach for replacing the multiple drop therapy.