Multiple iterations required to design ocular implants, which will last for the desired operational period of months or even years, necessitate the use of in-silico models for ocular drug delivery. In this study, we developed an in-silico model to simulate the flow of Aqueous Humor (AH) and drug delivery from an implant to the Trabecular Meshwork (TM). The implant, attached to the side of the intraocular lens (IOL), and the TM are treated as porous media, with their effects on AH flow accounted for using the Darcy equation. This model accurately predicts the physiological values of Intraocular Pressure (IOP) for both healthy individuals and glaucoma patients, as reported in the literature. Results reveal that the effective diffusivity of the drug within the implant is the critical parameter that can alter the bioavailability time period (BTP) from a few days to months. Intuitively, BTP should increase as effective diffusivity decreases. However, we discovered that with lower levels of initial drug loading, BTP declines when effective diffusivity falls below a specific threshold. Our findings further reveal that, while AH flow has a minimal effect on the drug release profile at the implant site, it significantly impacts drug availability at the TM.
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http://dx.doi.org/10.1016/j.xphs.2024.09.001 | DOI Listing |
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