Oral Delivery of Proteins and Peptides: Concepts and Applications - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 479

(gum) and the hard palate are keratinized, areas such as buccal, sublingual, and the
soft palate are nonkeratinized. Buccal epithelium thickness varies with location and
typically ranges from 500 m to 800

to 800 m in humans, dogs, and rabbits. The estimated
cell turnover time is 5-6 days [8,15] . Intercellular gap junctions are also present in
the buccal epithelium.
The mucosa of the oral cavity is divided into three functional zones. First, the
mucus-secreting regions (consisting of the soft palate, the floor of the mouth, the
undersurface of the tongue, and the labial and buccal mucosa) have a normally non-
keratinized epithelium. These regions represent the major absorption sites in the oral
cavity. Second, the hard palate and the gingiva are the regions of masticatory mucosa
and have a keratinized epidermis. Third, specialized zones are the borders of the lips
and the dorsal surface of the tongue with its highly selective keratinization.

10.2.1.2 Basement Membrane
The basement membrane forms a boundary between the basal layer of epithelium
and the connective tissues of the lamina propria and the submucosa. The basement
membrane is generally composed of extracellular materials. This membrane is fur-
ther divided into the lamina lucida, lamina densa, and a sublayer of fibrous material.
This layer generally provides adherence between epithelium and underlying connec-
tive tissues, mechanical support for epithelium and act as a barrier to the passage of
cells and some large molecules.

10.2.1.3 Connective Tissues
Connective tissues are further divided into the lamina propria and submucosa.
Connective tissue, in the form of a continuous sheet, composed of blood capillaries and
nerve fibers serving the oral mucosa, is known as lamina propria. Blood carried to the
oral mucosa is principally by way of the lingual, facial, and retromandibular veins.
These veins open into the internal jugular vein and thus avoid first-pass metabolism.
The buccal mucosae from monkeys, apes, dogs, pigs, and rabbits possess physiology
very similar to that of human buccal mucosa [8] .

10.2.2 Gastrointestinal Tract Other Than Oral Cavity
After administration of peptides and proteins to the gastrointestinal (GI) tract, their
absorption and other biochemical transformation largely depends on the variety of
GI tract parameters such as morphology, geometry, function of different components
of the cells, ultrastructure, biochemical processes, transport mechanisms, and hydro-
dynamics in the intestinal lumen.
Passage from the mouth to the anus (oropharynx, esophagus, stomach, small intes-
tine, and large intestine) and associated organs (salivary glands, liver, gallbladder, and
pancreas) compose a digestive system. Among all parts, the small intestine is the pri-
mary site of absorption for most drugs. The small intestine is further divided into three
parts: the duodenum, jejunum, and ileum. The large intestine, which is also called the