Transport Characteristics Of Epithelial Tissues

The normal expected mechanisms of corneal penetration is shown in Table 1 (8). Transport across epithelia occurs via two pathways: transcellular and paracellular. The former involves cell/tissue partitioning/diffusion, channel

Table 1 Expected Mechanisms of Corneal Penetration

Drug type

Apparent rate-limiting membrane

Mechanisms

Water soluble Epithelium

Low o/w partition into epithelium Slow diffusion through epithelium High partition rate + rapid diffusion through stroma/

endothelium Via leaky channels Solute movement may be

Water and oil Epithelium-stroma soluble Oil soluble Stroma intercellular and/or transcellular Both mechanisms operate

Ionizable

Epithelium + stroma or leaky channel

High o/w partition into epithelium Rapid diffusion through epithelium Mechanism not solely dependent upon partition coefficient

Source: Adapted from Ref. 8.

diffusion, and carrier-mediated transport. In contrast, the latter represents diffusive and convective transport occurring through intercellular spaces and tight junctions. Due to its aqueous nature, hydrophilic solutes would preferably adopt the paracellular pathway. However, there are three forms of junctional complexes that form between cells which hinder transport of hydrophilic molecules, namely, tight junctions (zonula occludens), intermediate junctions (belt desmosome or zonula adherens), and spot desmo-somes (macula adherens) (Fig. 3) (9). Among them, the tight junction is the uppermost and tightest, and it gives the greatest resistance for hydrophilic molecules to go between cells. The barrier property of the tight junction can be reflected by the transepithelial electrical resistance (TEER). The higher the TEER, the tighter the junctions that give a higher resistance for transport of molecules. Generally, epithelia with resistances in the range of 10100 ^ cm2 are considered leaky, whereas those with resistance ranging from 300 to 10,000 ^ cm2 are "tight." The cornea is generally classified as a moderately tight or moderately leaky tissue (400-1000 ^ cm2). A comparison of the electrophysiology and permeability of the cornea with other tissues is shown in Table 2 and 3, respectively (10).

The cornea also shows permselectivity (11). It has an isoelectric point (pi) of 3.2. At pHs above the pi, it carries a negative charge and is selective to positively charged molecules. On the other hand, at pHs below the pi, it microvilli .;: right jyrtctiin

knralln filament!

Jj^rnifj^jmoiorrva^ baoa) lo min a

Figure 3 Summary of the various cell junctions found in animal cell epithelia. (From Ref. 9.)

Jj^rnifj^jmoiorrva^ baoa) lo min a

Figure 3 Summary of the various cell junctions found in animal cell epithelia. (From Ref. 9.)

Table 2 Comparative Permeability Coefficients of Several Drugs Between Cornea and Other Tissues

Permeability coefficient (cm/s)

Permanent MW Rabbit/dog buccal Rabbit cornea Human skin

Water

Was this article helpful?

0 0

Post a comment