Optimization of Contact Lens Drug Delivery to Ocular Tissue
Barsoum, Kyrollos; Kureshi, Rakeeb; Lee, Carina; Pacifici, Noah
Intraocular pressure is a risk factor for developing glaucoma, a disease that damages the optic nerve and can result in vision impairment. Timolol is a beta-adrenergic antagonist that decreases intraocular pressure (IOP) by reducing the epithelial production of aqueous humor in the ciliary body. Traditionally, Timolol medication is administered with eye drops, but this treatment results in low corneal bioavailability and residence time of the drug in the ciliary muscle, making eye drops an inefficient method of drug delivery. In addition, eye drops lead to a higher concentration of Timolol in the systemic circulation, which can cause potential side effects. However, contact lenses soaked in Timolol solution can increase the bioavailability of the drug and drug release duration, therefore improving glaucoma treatment while decreasing the amount of drug absorbed into systemic circulation and unwanted side effects. The purpose of our study was to optimize the residence time of Timolol in the ciliary muscle at its effective concentration by optimizing the initial concentration in the soaked contact lens. We presented a model of drug diffusion from the contact lens through the cornea and aqueous humor to the ciliary body epithelium. Using COMSOL, the diffusion of Timolol through the contact lens, cornea, aqueous humor, and ciliary muscle was modeled using a mass transfer equation. Additionally, fluid flow and natural heat convection in the aqueous humor was accounted for in the model, and these governing equations were coupled to the equation for mass transfer of Timolol in the domain. The eye was simplified to a 2-dimensional axisymmetric spherical geometry. We aimed to solve for the optimal initial concentration of Timolol in the contact lens, given the ideal concentration in the ciliary body epithelium, which is a value that was found in the literature. In our 2-dimensional axisymmetric model, we demonstrated using our computer simulation that, in order to optimize the residence time of Timolol in the ciliary muscle at its most effective concentration, the initial concentration in the soaked contact lens must be 6.25 · 10−5 mol/m3. The mass diffusion of Timolol was not only driven by diffusion but also convective fluid flow. Fluid flow was introduced by a temperature gradient in the eye and resulted in a density gradient. Additionally, we performed several sensitivity analyses to determine which parameters affected the concentration of Timolol. Changing the ambient air temperature did not affect the uptake of Timolol in the ciliary muscle. The Peclet number indicates the importance of convection with respect to conduction and it was found to indicate that convection had a greater affect on Timolol transport than conduction. Additionally, the diffusivity of the contact lens also influenced the amount of Timolol delivered to the ciliary muscle. Thus, the concentration of Timolol in the ciliary muscle is highly sensitive to variations in convection and diffusivity parameters. In this model, we reinforced the validity of using computer simulations to model ocular drug delivery using a contact lens as a drug delivery platform. The parameters and variables of this model can be modified to account for different dosage requirements and different boundary or environmental conditions, making our model a viable way to speed up the design process by running the simulation instead of experimentally testing contact lenses with varying parameters. Our model is applicable to any drug that can be administered by contact lens and will reduce drug testing time and significantly reduce costs during the approval process.
Contact Lens; Drug Delivery; Ocular Tissue