Modulation of Intestinal Permeability: A Novel and Innovative Approach for the Oral Delivery of Drugs, Macromolecules and Antigens

In the past few years, we have witnessed an explosion in research aimed at creating new oral drug delivery systelns. This research has been fuelled by unprecedented challenges, such as the need to deliver newer and more complex dnlgs (such as proteins, hormones, etc.) that are becoming available through genetic engineering. Consequently, the need has arisen for further investigation into utilizing the intestine as a pritne site for targeting the absorption on these new compounds. One potential and attractive JnechaniSlll would be to exploit avenues that increase intestinal peJmeability. Theoretically, three transepitheJiaJ pathways are available for the passage of nlolecules fronl the intestinal lumen into the bloodstreanl (Figure 16.1): ( I) transcellular (ie through the cell) canier-mediated active or facil itated transport; (2) transcellular passive transport; and (3) paracellu]ur (ie between adjacent cells) transport With the exception of those molecules that are transported by active or facilitated transcellular mechanisms, the absorption of large hydrophilic macromolecules is mainly lim.ited to the paraceUular pathway (Lee et al., 1991). Under normal conditions, however, this pathway is restricted to molecules with molecular radii < II Angstroms and, therefore, is not accessible to large compounds. To overconle the intestinal barrier, several strategies have been developed to target either the transcellular or the paracellular pathway for drug delivery. The nlost