TY - JOUR
T1 - Computer modeling of drug delivery to the posterior eye
T2 - Effect of active transport and loss to choroidal blood flow
AU - Balachandran, Ram K.
AU - Barocas, Victor H.
PY - 2008/11
Y1 - 2008/11
N2 - Purpose. 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. 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) ×10-5 s-1, (2.0±0.35)×10-5 cm/s and 8.54×10-6 cm/s respectively. Conclusion. 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.
AB - Purpose. 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. 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) ×10-5 s-1, (2.0±0.35)×10-5 cm/s and 8.54×10-6 cm/s respectively. Conclusion. 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.
KW - Blood-vitreous barrier
KW - Fluorescein
KW - Fluorescein glucuronide
KW - Retinal pigment epithelium
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U2 - 10.1007/s11095-008-9691-3
DO - 10.1007/s11095-008-9691-3
M3 - Article
C2 - 18679772
AN - SCOPUS:53849107134
SN - 0724-8741
VL - 25
SP - 2685
EP - 2696
JO - Pharmaceutical research
JF - Pharmaceutical research
IS - 11
ER -