Other Routes of Protein and Peptide Delivery: Transdermal, Topical, Uterine, and Rectal - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 621

Paracellular route Transcellular route

Mucosal side

Passive diffusion Carrier-mediated transport

Endocytosis

Epithelial cell

Cell junction

Blood capillary

Lymph capillary

Serosal side

Figure 12.2 Pathways through SC.

pathway involves transport via the sweat glands or the pilosebaceous units (hair fol-
licles with their associated sebaceous glands). This route avoids penetration through
the SC and is therefore known as the shunt route. The transappendageal route is
considered to be of less significance than the transepidermal route for the reason of
its relatively very small area, approximately 0.1% of the total skin area. The rate of
success for transfer largely depends on the lipophilicity and the composition of the
entrant. Figure 12.2 shows pathways through the SC. The transcellular (intracellular)
route is important during electrically enhanced transport methods such as iontophore-
sis. Compounds that penetrate the SC via the transepidermal route may follow a trans-
cellular (intracellular) or intercellular pathway. Because of the highly impermeable
character of the cornified cells, the intercellular pathway is suggested as the route of
preference for most drug molecules [4] . Moreover, it was demonstrated that drug per-
meation across the SC increases many folds once the lipids are extracted [5] . Hence,
knowledge of the structure and physical properties of the intercellular lipids is vital
to broaden our insight into the skin's barrier role in permeation of therapeutics.

12.1.4 Approaches to Enhance Transdermal Peptide Delivery
12.1.4.1 Physical Approaches
12.1.4.1.1 Electrical Methods: Electroporation and Iontophoresis
As already discussed, proteins and peptides are poorly bioavailable when deliv-
ered orally and therefore are normally administered invasively by intravenous or