Oral Delivery of Proteins and Peptides: Concepts and Applications - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 486

the enterocyte into the circulation [41] . The process is saturable and utilized by small
hydrophilic molecules [42] .
10.3.4 Receptor-Mediated Transport
In receptor-mediated transport, drugs act either as a ligand for surface-attached recep-
tors or as a receptor for surface-attached ligands [43] . This process involves cell invagi-
nation, which leads to formation of a vesicle. This process, in general, is known as
endocytosis and comprises phagocytosis, pinocytosis, receptor-mediated endocytosis
(clathrin mediated), and potocytosis (nonclathrin mediated) [44] . Small peptides such
as di- and tri-peptides, as well as monosaccharides and amino acids, are thought to
be transported by carrier-mediated systems [8,45,46] . After a drug is absorbed in the
GI tract, it gains access to the systemic circulation via two separate and functionally
distinct absorption pathways: portal blood and the intestinal lymphatics. The physico-
chemical and metabolic features of the drug and the characteristics of the formulation
largely control the relative proportion of drug absorbed via these two pathways. Portal
blood represents the major pathway for the majority of orally administered drugs as
it has higher capacity to transport both water-soluble and poorly water-soluble com-
pounds. During this process, hydrophilic molecules are carried to the liver via the
hepatic portal vein, and then by the hepatic artery gain access to the systemic circula-
tion, for subsequent delivery to their sites of action. On the other hand, highly lipophilic
drugs (log P  5) that cross the same epithelial barrier are transported to the intestinal
lymphatics, which directly deliver them to the vena cava, thereby bypassing the hepatic
first-pass metabolism [47] .
10.4 Barriers to Protein Absorption
Protein and peptide delivery via oral route is a keen area of research. The main draw-
backs that should be considered during development of such a delivery system are
barriers to protein absorptions. Such barriers include the mucus barrier, extracellular
barriers, enzymatic barriers, and cellular barriers [48] . These barriers restrict the bio-
availability of the orally given peptides to less than 1%. The ray of hope here is that
there are some exceptions in which some proteins show higher bioavailability alone
or in the presence of certain adjuvants.
10.4.1 Mucus Barrier
The glycocalyx, which is atop the epithelial cells, is a fuzzy and filamentous coat
that is weakly acidic and consists of sulfated mucopolysaccharides. Goblet cells
secrete mucus, which lines the top of the glycocalyx [49] . The mucus consists of
mucin glycoproteins, enzymes, electrolytes, water, and so forth [50] . The cohesive
and adhesive nature of the mucus layer is due to the presence of mucin glycoprotein
[51,52] . Mucus and glycocalyx layers are the first and foremost barriers to peptides