(584c) Sustained In Vivo Release From Imprinted Daily Wear Contact Lenses

Ocular tear flow poses a significant challenge to effective and efficient delivery of drugs to the eye. Typically, less than 1-7% of drug delivered through eye drop formulations is absorbed. However, eye drops and ointments account for 90% of ophthalmological formulations on the market today. Thus, there exists a considerable unmet need and strong motivation for more efficacious delivery of ocular therapeutics. Molecular imprinting is an effective technique to create macromolecular memory within a polymer, allowing greater control of drug transport from hydrogels. Imprinted lenses can deliver a constant drug concentration at a high effectiveness level for extended periods leading to significantly increased duration of action. The enormous advantage of using imprinting mechanisms is that the release rate, and thus the concentration reached, can be altered by changing the engineering design of such systems.

In this work, we demonstrate the successful in vivo extended release of a small molecular weight therapeutic, ketotifen fumarate (MW=425), from molecularly imprinted, therapeutic contact lenses. This is the first time that a steady, effective concentration of drug is maintained in the tear film from a contact lens for an extended period of time for the entire duration of lens wear. Poly(HEMA-co-AA-co-AM-co-NVP-co-PEG200DMA) soft contact lenses were prepared (100±5µm thickness, diameter 11.8 mm, power zero), and a constant tear film concentration of 170±30 μg/mL was measured for up to 26 hours in a New Zealand white rabbit model. The results showed a dramatic increase in ketotifen mean residence time (MRT) and bioavailability compared to topical drop therapy and drug soaked lenses. The MRT for imprinted lenses was 12.47±3.99 hours, almost 37.0 fold greater than 0.035% eye drops (Zaditor®). Furthermore, the bioavailability (AUC_0-26hrs) was 127 fold greater for imprinted lenses than topical eye drops. The results indicate that molecular imprinting provides an exciting rational engineering strategy for sustained release. It is clear from this work that imprinted lenses are very promising combination devices and are much more effective and efficient delivery devices than eye drops.