(500f) Extended Ophthalmic Drug Delivery by Silicone-Hydrogel Contact Lenses

Ophthalmic drug delivery via eye drops is inefficient as only 1-5% of the applied drug enters the cornea and the rest is absorbed into the bloodstream. This absorbed drug then enters other organs where it can cause side effects. Furthermore, application of ophthalmic drugs as drops results in a rapid variation in drug delivery rates to the cornea that limits the efficacy of therapeutic systems and limit compliance. On the other hand, ophthalmic drug delivery via soft contact lenses has been widely studied due to its high degree of comfort, biocompatibility, and significant increase in drug residence time and bioavailability. However, a majority of the drugs taken up by the commercial contact lenses is released in a very short period of time, which is not suitable for extended drug delivery. The purpose of our research is to develop soft contact lenses for long term and controlled drug delivery.

This talk will focus on two novel methods for developing extended-wear, extended-release contact lenses. The first approach focuses on development of new silicone-hydrogel materials that satisfy all requirements for contact lenses, yet provide extended drug release. The second approach focuses on creating transport barriers within commercial contact lenses such that an included drug is forced to take a long tortuous path to diffuse from the gel matrix. In the absence of diffusion barriers, drug molecules diffuse out of the lens in about an hour. In contrast, if diffusion barriers that have negligible affinity to the included drug are placed in the gel matrix, molecules have to diffuse around these barrirers, resulting in an increase in the path length and the release duration. In this talk we will focus on using a hydrophobic nutraceutical oil Vitamin E as the diffusion barrier material. This liquid phase diffusion barrier can be loaded into the contact lens by dissolving Vitamin E in ethanol that swells the contact, leading to a high concentration of the barrier forming liquid above its solubility limit in the lens material after the solvent evaporated. This method provides advantage of loading diffusion barriers after the hydrogel matrix is formed.

Novel silicone hydrogel lenses developed in our lab meet all requirements of contact lenses and yet release timolol and dexamethasone for more than 2 weeks. Furthermore, incorporation of Vitamin E into commercial lenses significantly reduces drug diffusivity. For timolol release by commercial silicone-hydrogel contact lens, A 10% Vitamin E loading increases release time by a factor of about 5 and a 40% loading increase release time by a factor of as high as about 400 for Night & DayTM lens. The timolol release time increase is quadratic in the amount of Vitamin E loading, and a scaling model was developed for this process. Similar results have been obtained for other hydrophilic drugs including fluconazole and dexamethasone 21-disodium phosphate (DXP). The effect of the Vitamin E diffusion barrier is smaller but still significant for release of hydrophobic drugs such as dexamethasone (DX) and ketotifen fumarate (KF).

Contact lenses with diffusion barriers are promising candidates for ophthalmic drug delivery. These can significantly improve the drug delivery profiles, reduce wastage and minimize side effects. Also these approaches can be used to deliver lubricating agents to minimize contact lens mediated dry eyes.