Drug delivery studies in Caco-2 monolayers. III. Intestinal transport of various vasopressin analogues in the presence of lysophosphatidylcholine

The transport of a series of vasopressin and oxytocin analogues with varying lipophilicities was studied in Caco-2 monolayers. Transport was studied across the bare monolayer and after treatment with a phospholipid absorption enhancer, palmitoyl lysophosphatidylcholine. The range in lipophilicity of the analogues, estimated as the capacity factor, was found to be from 0.19 to 3.43. The intrinsic transport of the peptides across Caco-2 monolayers was found to be low. The apparent permeability coefficients, P_app, were in the range of 2 × 10^-8-6 × 10⁷ cm/s. However, peptide transport was significantly greater (P_app in the range of 5 × 10^-6-2 × 10^-5 cm/s) when facilitated by addition of palmitoyllysophosphatidylcholine. The results suggest that polypeptide transport across Caco-2 monolayers does not depend on lipophilicity, but that the facilitated transport does depend on the lipophilicity.