Finite Element Design Optimization of a Hyaluronic Acid-Based Hydrogel Drug Delivery Device for Improved Retention

摘要

Drug-loaded hydrogel devices are emerging as an effective means of localized and sustained drug delivery for the treatment of corneal conditions and injuries. One such device uses a novel, thiolated crosslinked carboxymethylated, hyaluronic acid-based hydrogel (CMHA-S) film to deliver drug to the ocular surface upon placement into the inferior fornix of the eye. While proven to be very safe and effective, the CMHA-S film tends to dislodge in the highly-lubricated ocular environment, thereby reducing drug delivery efficiency and drug efficacy. In this study, we used a three-dimensional computational finite element model of the eye to determine the effect of geometry and surface friction on film retention in the inferior fornix, and to evaluate multiple geometrical film designs. Retention of the film was dependent on geometry and on the friction ratio of the film to the eyelid and globe. These effects were interactive. When the ratio of friction on the lid side to the globe side of the film was low, geometry played a large role in the film's displacement. When this ratio was high, differences in displacement due to geometry were negligible. The optimal relationship of friction between the film and its eyelid-side and globe-side surfaces was found to be linear with at least 1.4 times greater friction required on the eyelid-side for immobilization. A geometry similar to a half cylinder was found to be most effective with this friction ratio in retaining the film in the inferior fornix and in contact with the globe. Other geometries will likely require other friction ratios. In summary, CMHA-S film retention can be achieved through simple modifications of geometry and manipulation of surface interaction with the eye.