Oral Delivery of Proteins and Peptides: Concepts and Applications - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 478

dosage form without any pain or discomfort. These features increase patient compli-
ance and acceptance of the dosage form [9,10] . Due to routine exposure to a variety
of foreign substances, oral mucosa becomes robust and thus less prone to irreversible
irritation or damage by the drug, the dosage form, or additives such as absorption pro-
moters. However, salivary production and composition may contribute to chemical
modification of certain drugs [11,12] . Protein and peptide absorption increases several
fold due to the presence of a great number of capillary blood vessels, lymphatic plexus,
and Peyer's patches.
Oral bioavailability below 1% is often recorded for proteins and peptides because
of limiting factors such as inactivation due to stomach acid or to digestive protease
enzymes, the larger size and hydrophilic nature of protein, the tendency to undergo
denaturation and aggregation, and first-pass metabolism [13-15] . To overcome such
problems, various approaches are useful, that is, site-specific drug delivery [16,17] ,
chemical modification [18,19] , use of some vehicles and adjuvants [20] , bioadhesive
drug delivery [21,22] , use of penetration enhancers, protease inhibitors [23] , nano
and microparticulate carriers [24] , and use of multifunctional polymeric excipients
[25] . New tools that raise the membrane permeability of macromolecules have been
incorporated into delivery systems; this is essential to attain the high oral bioavail-
ability required for acceptance in clinical applications. Modification of the physi-
cochemical properties of macromolecules [26] , the addition of novel function to
macromolecules, and the use of modified and specialized delivery carriers [27,28]
improves the oral bioavailability from 1% to at least 30-50%. More importantly, it is
essential that these approaches maintain the biological activity of the proteins.
The purpose of the chapter is to focus attention on factors affecting protein and
peptide absorption, barriers to protein absorption, penetration pathways, various
approaches to improve their oral delivery, methods to study oral absorption, and vari-
ous strategies in oral immunization.
10.2 Anatomy and Physiology of Oral Mucosa
10.2.1 Oral Cavity
The oral cavity is composed of three tissue layers: the epithelium, the basement
membrane, and connective tissues.
10.2.1.1 Epithelium
The epithelium is composed of epithelial cells originated from a layer of cuboi-
dal-shaped basal cells. Approximately 40-50 layers of stratified squamous epithe-
lial cells make up the epithelium. These layers were made because the basal cells
undergo continuous mitosis and move to the surface. As the cells migrate to the sur-
face through the intermediate layers, they differentiate and become larger, flattened,
and surrounded by an external lipid matrix (membrane-coating granules). This exter-
nal lipid matrix determines the drug permeability of the tissue. Although gingiva