The effect of polyethylene glycol molecular weight on corneal transport and the related influence of penetration enhancers

In order to understand the mechanism of olecular weight dependence on corneal transport of solutes, it is important to separate charge type and molecular size, two major parameters for peptide delivery. The transport characteristics of a series of different molecular weight polyethylene glycols (PEGs), which are hydrophilic and uncharged, were measured in vitro. The absorption of PEGs exhibited a dependence on the molecular weight with a cutoff between PEG 400 and PEG 600. The effect of penetration enhancers, including a bile salt, digitonin, and cytochalasin B, on the molecular weight permeability profile can be used to identify mechanisms of penetration enhancement. Bile salt did not alter the molecular weight permeability profile. In contrast, digitonin greatly increased absorption of the PEGs and selective molecular weight effects were seen with cytochalasin B. Correlation of mucosal integrity with the effectiveness of the penetration enhancer indicates that cytochalasin B acts on the tight junction by opening intercellular spaces. These results indicate that the paracellular pathway may play an important role in hydrophilic, large molecule transport through the cornea.