Virtual pharmacokinetic model of human eye.

A virtual pharmacokinetic 3D model of the human eye is built using Comsol Multiphysics® software, which is based on the Finite Element Method (FEM). The model considers drug release from a polymer patch placed on sclera. The model concentrates on the posterior part of the eye, retina being the target tissue, and comprises the choroidal blood flow, partitioning of the drug between different tissues and active transport at the retina pigment epithelium (RPE)-choroid boundary. Although most straightforward, in order to check the mass balance, no protein binding or metabolism is yet included. It appeared that the most important issue in obtaining reliable simulation results is the finite element mesh, while time stepping has hardly any significance. Simulations were extended to 100,000 s. The concentration of a drug is shown as a function of time at various points of retina, as well as its average value, varying several parameters in the model. This work demonstrates how anybody with basic knowledge of calculus is able to build physically meaningful models of quite complex biological systems.

[1]  R. Hinton,et al.  First principles. , 2016, The Pharos of Alpha Omega Alpha-Honor Medical Society. Alpha Omega Alpha.

[2]  E. Toropainen,et al.  Paracellular and passive transcellular permeability in immortalized human corneal epithelial cell culture model. , 2003, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[3]  Milica Radisic,et al.  Mathematical model of oxygen distribution in engineered cardiac tissue with parallel channel array perfused with culture medium containing oxygen carriers. , 2005, American journal of physiology. Heart and circulatory physiology.

[4]  A. Urtti,et al.  Permeability of retinal pigment epithelium: effects of permeant molecular weight and lipophilicity. , 2005, Investigative ophthalmology & visual science.

[5]  E. Ng,et al.  Targeting angiogenesis, the underlying disorder in neovascular age-related macular degeneration. , 2005, Canadian journal of ophthalmology. Journal canadien d'ophtalmologie.

[6]  A. Subrizi,et al.  Barrier analysis of periocular drug delivery to the posterior segment. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[7]  Benita J. O’Colmain,et al.  Prevalence of age-related macular degeneration in the United States. , 2004, Archives of ophthalmology.

[8]  P. McDonnell,et al.  Nanoparticle diffusion in, and microrheology of, the bovine vitreous ex vivo. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[9]  B. Saville,et al.  Finite element modeling of drug distribution in the vitreous humor of the rabbit eye , 1997, Annals of Biomedical Engineering.

[10]  Kakuji Tojo,et al.  A pharmacokinetic model for ocular drug delivery. , 2004, Chemical & pharmaceutical bulletin.

[11]  P. Santi,et al.  Effect Of Formulation Factors On The Trans-scleral Iontophoretic Transport Of A 40kDa Dextran In-vitro , 2011 .

[12]  A. Urtti,et al.  Ocular Pharmacokinetic Modeling Using Corneal Absorption and Desorption Rates from in Vitro Permeation Experiments with Cultured Corneal Epithelial Cells , 2003, Pharmaceutical Research.

[13]  K. Tojo,et al.  Pharmacokinetic model of intravitreal drug injection. , 1994, Mathematical Biosciences.

[14]  M. Saadatmand,et al.  Computer Modeling of Drug Distribution after Intravitreal Administration , 2011 .

[15]  P. Santi,et al.  Effect of formulation factors on the trans-scleral iontophoretic and post-iontophoretic transports of a 40 kDa dextran in vitro. , 2011, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[16]  Veli-Pekka Ranta,et al.  Transscleral drug delivery to the posterior eye: prospects of pharmacokinetic modeling. , 2006, Advanced drug delivery reviews.

[17]  E. Y. K. Ng,et al.  Bioheat transfer in the human eye : a boundary element approach , 2006 .

[18]  Arunn Narasimhan,et al.  Effect of choroidal blood flow on transscleral retinal drug delivery using a porous medium model , 2012 .

[19]  M. Prausnitz,et al.  Permeability of cornea, sclera, and conjunctiva: a literature analysis for drug delivery to the eye. , 1998, Journal of pharmaceutical sciences.

[20]  A. Urtti,et al.  Neural retina limits the nonviral gene transfer to retinal pigment epithelium in an in vitro bovine eye model , 2004, The AAPS Journal.

[21]  Robert Langer,et al.  First-principles, structure-based transdermal transport model to evaluate lipid partition and diffusion coefficients of hydrophobic permeants solely from stratum corneum permeation experiments. , 2007, Journal of pharmaceutical sciences.

[22]  P. Jong.  Prevalence of age-related macular degeneration in the United States. , 2004 .

[23]  M. Antopolsky,et al.  Effect of iontophoresis on the in vitro trans-scleral transport of three single stranded oligonucleotides. , 2013, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[24]  Nam Sun Wang,et al.  Study of Ocular Transport of Drugs Released from an Intravitreal Implant Using Magnetic Resonance Imaging , 2005, Annals of Biomedical Engineering.

[25]  A. Urtti,et al.  Vitreous Is a Barrier in Nonviral Gene Transfer by Cationic Lipids and Polymers , 2003, Pharmaceutical Research.

[26]  H. J. Wyatt.  Modelling Transport in the Anterior Segment of the Eye , 2004, Optometry and vision science : official publication of the American Academy of Optometry.

[27]  Victor H. Barocas,et al.  Computer Modeling of Drug Delivery to the Posterior Eye: Effect of Active Transport and Loss to Choroidal Blood Flow , 2008, Pharmaceutical Research.