DRUG-DELIVERY STUDIES IN CACO-2 MONOLAYERS .2. ABSORPTION ENHANCER EFFECTS OF LYSOPHOSPHATIDYLCHOLINES

This paper concerns the mechanistic elucidation of a certain class of absorption enhancers within the group of phospholipids, lysophosphatidylcholines. The studies were performed in Caco-2 monolayers. Physico-chemical characteristics and effects on the integrity and viability of the Caco-2 monolayers were found to be correlated with the absorption promoting effects of the phospholipids. Comparing enhancers with varying size of the lipophilic moiety, the lipophilicity was shown to be of the utmost importance for all of the observed effects. As the chain length increased from 6 to 16 methylene groups, the effects measured on the monolayers were amplified. The acute effects were evaluated by various microscopic staining techniques as well as by transport studies. The transport rates of the vasopressin analogue 1-deamino-8-D-arginine-vasopressin (DDAVP) were determined as a measure of the monolayer integrity. Based on the apparent permeability coefficient, P-app, it could be concluded that phospholipid treatment increased DDAVP transport even under circumstances where the cell monolayer integrity was only slightly altered.