Marko Lamminsalo1, Ella Taskinen2, Timo Karvinen3, Astrid Subrizi4, Lasse Murtomäki5, Arto Urtti2,6,7, Veli-Pekka Ranta2. 1. School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70210, Kuopio, Finland. marko.lamminsalo@uef.fi. 2. School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70210, Kuopio, Finland. 3. Comsol Oy, Helsinki, Finland. 4. Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark. 5. Department of Chemistry and Materials Science, Aalto University, Espoo, Finland. 6. Faculty of Pharmacy, Drug Research Program, University of Helsinki, Helsinki, Finland. 7. St Petersburg State University, Petergoff, St. Petersburg, Russian Federation.
Abstract
PURPOSE: To extend the physiological features of the anatomically accurate model of the rabbit eye for intravitreal (IVT) and intracameral (IC) injections of macromolecules. METHODS: The computational fluid dynamic model of the rabbit eye by Missel (2012) was extended by enhancing the mixing in the anterior chamber with thermal gradient, heat transfer and gravity, and studying its effect on IC injections of hyaluronic acids. In IVT injections of FITC-dextrans (MW 10-157 kDa) the diffusion though retina was defined based on published in vitro data. Systematic changes in retinal permeability and convective transport were made, and the percentages of anterior and posterior elimination pathways were quantified. Simulations were compared with published in vivo data. RESULTS: With the enhanced mixing the elimination half-lives of hyaluronic acids after IC injection were 62-100 min that are similar to in vivo data and close to the theoretical value for the well-stirred anterior chamber (57 min). In IVT injections of FITC-dextrans a good match between simulations and in vivo data was obtained when the percentage of anterior elimination pathway was over 80%. CONCLUSIONS: The simulations with the extended model closely resemble in vivo pharmacokinetics, and the model is a valuable tool for data interpretation and predictions.
PURPOSE: To extend the physiological features of the anatomically accurate model of the rabbit eye for intravitreal (IVT) and intracameral (IC) injections of macromolecules. METHODS: The computational fluid dynamic model of the rabbit eye by Missel (2012) was extended by enhancing the mixing in the anterior chamber with thermal gradient, heat transfer and gravity, and studying its effect on IC injections of hyaluronic acids. In IVT injections of FITC-dextrans (MW 10-157 kDa) the diffusion though retina was defined based on published in vitro data. Systematic changes in retinal permeability and convective transport were made, and the percentages of anterior and posterior elimination pathways were quantified. Simulations were compared with published in vivo data. RESULTS: With the enhanced mixing the elimination half-lives of hyaluronic acids after IC injection were 62-100 min that are similar to in vivo data and close to the theoretical value for the well-stirred anterior chamber (57 min). In IVT injections of FITC-dextrans a good match between simulations and in vivo data was obtained when the percentage of anterior elimination pathway was over 80%. CONCLUSIONS: The simulations with the extended model closely resemble in vivo pharmacokinetics, and the model is a valuable tool for data interpretation and predictions.
Authors: Hyuncheol Kim; Martin J Lizak; Ginger Tansey; Karl G Csaky; Michael R Robinson; Peng Yuan; Nam Sun Wang; Robert J Lutz Journal: Ann Biomed Eng Date: 2005-02 Impact factor: 3.934
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