Computer modeling of drug delivery to the posterior eye: effect of active transport and loss to choroidal blood flow.
OBJECTIVE
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.


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.


RESULTS
The volumetric choroidal loss constant, mass transfer coefficient from the scleral surface and active transport component were evaluated to be (2.0 +/- 0.6) x 10(-5) s(-1), (2.0 +/- 0.35) x 10(-5) cm/s and 8.54 x 10(-6) cm/s respectively.


CONCLUSIONS
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.
Balachandran
Ram K
RK
Department of Mechanical Engineering, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Barocas
Victor H
VH
D001693:Biological Transport, Active; D002829:Choroid / Q000098:blood supply*; D003198:Computer Simulation; D016503:Drug Delivery Systems; D005123:Eye / Q000378:metabolism*; D012039:Regional Blood Flow; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism