Intestinal permeation enhancers to improve oral bioavailability of macromolecules: reasons for low efficacy in humans.

Permeation enhancement is most effective when the PE is co-localized with the macromolecule at the epithelial surface. Conditions in the GI tract impede optimal co-localization. Novel delivery systems that limit dilution and spreading of the PE and macromolecule in the small intestine have attempted to replicate promising enhancement efficacy observed in static drug delivery models.