Mathematical Modeling of Drug Release from Bi-Layered Drug Delivery Systems in the Eye

Eduardo A. Chacin Ruiz

University at Buffalo, The State University of New York, Buffalo, NY

"Mathematical Modeling of Drug Release from Bi-Layered Drug Delivery Systems in the Eye"

Wet age-related macular degeneration (AMD) is a blinding chronic eye disease commonly treated with monthly intravitreal injections. Drug delivery systems (DDS) aim to reduce injection frequency. Here, we developed mathematical models of drug release from bi-layered prototype chitosan-polycaprolactone (PCL) DDS to help optimize their design and improve wet AMD treatments. Fick’s second law is used to model the unsteady-state drug release from DDS into phosphate buffer saline. For drug-loaded chitosan-PCL microspheres, we solved the diffusion equation numerically using finite differences in MATLAB, and finite elements in COMSOL. We then use COMSOL for modeling a more complicated geometry consisting of a chitosan-PCL cylindrical device with a hollow core for drug loading. Furthermore, we use ordinary least squares objective functions in both software to estimate relevant parameters from the DDS using experimental data. Our MATLAB and COMSOL models accurately simulated the cumulative drug release behavior from the microspheres for 160 days compared to in vitro experimental data. For the cylindrical device, we observed large deviations in the initial 50 days, with more accurate predictions after that, implying other drug-release mechanisms, like erosion, need to be considered for the initial phase. The models can help optimize the design of bi-layered DDS to improve wet AMD treatments and provide insights into the mechanisms involved in the drug release from these DDS.
Additional authors: Jabia M. Chowdhury (1); Katelyn E. Swindle- Reilly (2,3); Ashlee N. Ford Versypt (1) (1) Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY (2) William G. Lowrie Department of Chemical and Biomolecular Engineering, Ohio State University, Columbus, OH (3) Department of Biomedical Engineering, Ohio State University, Columbus, OH

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