Intestinal permeation enhancers: Lessons learned from studies using an organ culture model

Permeation enhancers (PEs) are compounds aimed to increase intestinal uptake of oral drugs with poor bioavailability. This mini-review focuses on results recently obtained with PEs using an intestinal organ culture model. The model predicts which paracellular/transcellular pathways across the epithelium are susceptible to different classes of PEs (mainly surfactants and cell penetrating peptides). PEs: 1) generate a transmembrane transcellular pathway, 2) block apical endocytosis (first step in apical-to-basolateral transcytosis), and 3) perturb normal cell membrane integrity. The results argue that surfactants and cell penetrating peptides are not suitable for use in formulations aimed to exploit transcytosis in oral drug delivery.