The sequential barriers of epithelium, stroma and, to a lesser extent, the endothelium pose difficulties for drug absorption through the cornea (Figure 11.2). The epithelial and endothelial cells are rich in lipids and are mostly permeable to fat soluble substances. The stroma is acellular with a high water content, making it permeable to water soluble substances. In order for drugs to be well absorbed, they need to have a mixed hydrophilic/ hydrophobic nature with an intermediate partition coefficient in the range of 10 to 100.
The stroma can be considered as a single compartment with the aqueous humor since the endothelium separating them is only a weak barrier and hence is not rate limiting. Both the epithelium and the aqueous tissues can act as drug reservoirs. The hydrophilic stroma serves as a depot for water-soluble compounds such as catecholamines and their metabolites, whereas the epithelium is the main depot for lipophilic molecules such as chloramphenicol.
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