Computational Study of Hydrogel Ring Device for Ocular Drug Delivery
Hanif, Sarah; Lim, Abigail; Sit, Hilarie; Tan, Wan Qing Melissa
Researchers have developed many different kinds of ocular drug delivery devices. However, most address anterior eye disorders—very few are designed specifically for the treatment of posterior eye diseases. A recently-developed hydrogel ring device is capable of delivering therapeutic quantities of the drug Ofloxacin to treat ocular infections at the back of the eye—a region typically difficult to access via systemic (e.g. ingestion of pills) and topical (e.g. eye drops) methods. Despite promising preliminary in vivo test results, much remains unknown about the precise drug transport pathway from the hydrogel ring to the posterior segment of the eye, as well as how design parameters may be altered to increase drug delivery efficiency. The aim of this work is to fully characterize the drug release and transport characteristics from the hydrogel, to ocular tissues (anterior and posterior), as well as provide a quantitative method for the optimization of various hydrogel ring design parameters. To achieve the abovementioned goals, we built a computational model using COMSOL Multiphysics to simulate the release of Ofloxacin from the hydrogel ring and to obtain the resulting drug distribution in ocular tissues at various time points. Using the model, we monitored the transient Ofloxacin concentration profile over the entire eye, for a treatment period of ten hours. Our results showed that while Ofloxacin diffuses to the anterior region much more quickly than to posterior tissues, Ofloxacin concentrations do successfully accumulate to therapeutic levels in the posterior tissues during the simulated ten-hour treatment period. This finding supports the therapeutic potential of the hydrogel ring for the treatment of posterior eye diseases. We also performed optimization analyses to determine the ideal set of hydrogel ring design parameters for the treatment of infections caused by three bacterial species commonly associated with ocular disorders: Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. Preliminary findings suggest that the combination of an initial mass of 3 mg/m3 of Ofloxacin in the hydrogel and an Ofloxacin diffusivity of 3.11X10−9 m2/s in the hydrogel provide the best possible therapeutic outcome (from the range of values tested) for the treatment of E. coli and S. aureus infections. To our best knowledge, there is no existing computational model that simulates drug transport through the entire human eye from an ocular drug delivery device. We believe that our computational model will be highly useful for quantitative device characterization of the hydrogel ring, as well as in the optimization of the hydrogel ring design for the treatment of posterior eye disorders. This work may also serve as a model and reference for future computational work on ocular pharmacokinetics and/or ocular drug delivery devices.
ocular drug delivery, hydrogel, ocular ring, computational model, finite element analysis, COMSOL, ocular pharmacokinetics