Computer Modeling of Drug Delivery to the Posterior Eye: Effect of Active Transport and Loss to Choroidal Blood Flow
The direct penetration route following transscleral drug administration presents several barrier and clearance mechanisms—including loss to choroidal blood flow, active transport by the retinal pigment epithelium (RPE), and loss to the conjunctival lymphatics and episcleral blood vessels. The objective of this research was to quantify the role of choroidal and episcleral losses.
Materials and Methods
A finite element model was created for drug distribution in the posterior human eye. The volumetric choroidal loss constant, active transport component and mass transfer from the scleral surface were unknown parameters in the model. The model was used to simulate drug distribution from a systemic source, and the results were compared to existing experimental results to obtain values for the parameters.
The volumetric choroidal loss constant, mass transfer coefficient from the scleral surface and active transport component were evaluated to be (2.0 ± 0.6) × 10−5 s−1, (2.0 ± 0.35) × 10−5 cm/s and 8.54 × 10−6 cm/s respectively.
Loss to the choroidal circulation was small compared to loss from the scleral surface. Active transport was predicted to induce periscleral movement of the drug, resulting in more rapid distribution and elevated drug concentrations in the choroid and sclera.
KEY WORDSblood–vitreous barrier fluorescein fluorescein glucuronide retinal pigment epithelium
This work was supported by the Institute for Engineering and Medicine (IEM) at the University of Minnesota and by the National Institutes of Health (R03-EB007815). The resources provided by the Minnesota Supercomputing Institute (MSI) at the University of Minnesota were used for running the simulations. We thank Phil Bransford, who helped us in the initial stages of model building and Matt Stay for providing valuable insights on the subject matter.
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