Abstract
Purpose: :
To evaluate the roles of the barriers of periocular drug delivery to the retina and vitreous.
Methods: :
The barriers were evaluated by using kinetic simulations that were based on experimental data. The permeability data of the isolated sclera and retinal pigment epithelium (RPE) were collected. The transfer rate of compounds from chorioidea to the plasma was calculated based on in vivo experiments. The sclera and RPE permeability were incorporated to the model as well as the drug clearance from the chorioidea. The model was built using STELLA simulation software and it includes sclera, chorioidea and RPE. Clearance by the chorioidea was estimated using diffusivity in the tissue and porosity of the capillaries.
Results: :
The model describes accurately the individual barriers (sclera, chorioidea, RPE). The simulations with the complete model with all components reveal that the role of sclera as barrier is not substantial. The role of chorioidea is significant as most of the drug is cleared by the the blood flow. RPE is significant barrier particularly for the hydrophilic drugs. The model was used to simulate drug concentrations in the chorioidea and retina.
Keywords: retinal pigment epithelium • choroid • sclera