(709f) Vitamin E Loaded Contact Lenses for Extended Ophthalmic Drug Delivery

The extended wear soft contact lenses comprise of bicontinuous phases of silicon and hydrogel materials to maximize oxygen and ion permeabilities. These lenses are also being explored as vehicles for extended delivery of ophthalmic drugs. Ophthalmic drugs are typically delivered via eye drops that are inefficient as less than 5% of the applied drug enters the target tissues, while the remaining enters systemic circulation and other tissues. Contact lenses allow increased bioavailability by increasing the residence time of drugs in tears. However, a majority of the drugs loaded into the contact lenses is released in a very short period of time, which is undesirable for extended drug delivery. This talk will focus on a novel approach for manipulating the transport properties of the thin silicon-hydrogel films (contact lenses) by incorporation of nanobarriers of Vitamin E into the films. The presence of the barriers will increase the tortuosity of the lens for hydrophilic drugs leading to increased release durations.

The hydrophobic nutraceutical oil Vitamin E is loaded into silicone hydrogel contact lenses by soaking the lenses in a solution of Vitamin E in ethanol. After equilibration, the lenses are withdrawn from the ethanol solution and soaked in water to extract the ethanol. Since Vitamin E is insoluble in water, it remains in the lens, and phase separates into nanosized aggregates. Hydrophlilic drugs such as timolol, fluconazole and dexamethasone 21-disodium phosphate (DXP) have a negligible affinity for Vitaim E. Thus, these molecules diffuse out of the gel matrix through a tortuous path around the barriers, which leads to an increase in release duration. On the other hand, hydrophobic drugs, such as dexamethasone (DX), partitions and diffuse through Vitamin E and thus the effect of Vitamin E inclusion on hydrophobic drugs is different than on the hydrophilic drugs. While the mechanisms are expected to be different, Vitamin E inclusion could attenuate transport of hydrophobic drugs as well due its high viscosity, which will lead to reduced diffusivity.

Prior to exploring the effect of Vitamin E loading on drug release profiles, several other lens' properties including geometry, ion permeability, oxygen permeability and UV transmittance were measured to determine the pros and cons of loading Vitamin E into the lenses. The results indicate the changes in relevant properties caused by Vitamin E loading are relatively small, and do not disqualify these silicone hydrogels from functioning as extended-wear contact lenses. For example, Vitamin E loading in the Night & DayTM lens leads to slight increase in lens sizes (6.5% increase for 30% loading), a slight reduction in oxygen diffusion (about 30% reduction for 75% loading), and a more significant reduction in the ion permeability (50% reduction for 10% loading). In addition, Vitamin E loading has a beneficial effect of blocking UV radiation which will reduce the corneal damage due to UV light.

In vitro drug release results show that the increase in release duration is quadratic for hydrophilic drugs in Vitamin E loading. For example, for NIGHT&DAYTM lens loadings of 10 and 40% Vitamin E increase release time of timolol by a factor of about 5 and 400, leading to total release durations of about 0.5 and 16, days, respectively. Similar results have been obtained for other hydrophilic drugs such as DXP and fluconazole as well. For hydrophobic DX, the effect of the Vitamin E inclusion is smaller but still significant for release. For instance, with about 30% of Vitamin E loading in the contact lens, the DX release time can be increased to 7 to 9 days for ACUVUE® OASYS?, NIGHT&DAY? and O2OPTIX?, which is a 9 to 16 fold increase compared to the DX release duration by pure contact lens without Vitamin E loading. The ophthalmic drugs delivery by contact lens can be viewed as a one-dimensional transport by a flat thin film, and subsequent mathematical models based on the earlier proposed mechanisms for both hydrophilic and hydrophobic drugs were established.

Silicone hydrogel contact lenses with Vitamin E are promising candidates for extended ophthalmic drug delivery. These Vitamin loadings can significantly attenuate the drug delivery rate, reduce wastage and provide safer treatment route. Also these approaches can be used to deliver lubricating agents to minimize contact lens mediated dry eyes. The approach of creating nanosized diffusion barriers could also be useful in several other applications.