Oral Delivery of Proteins and Peptides: Concepts and Applications - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 481

which is mainly responsible for the digestive and absorptive functions of the small
intestine. The surface area of mucosal layer is increased by several more folds than
predicted for a simple cylinder due to the presence of circular folds, fingerlike pro-
jections called villi, and depressions called crypts. The mucosal surface area of the
small intestine is approximately 250 m 2 , whereas the simple cylinder has the surface
area of 0.5 m 2 . The height of each villi is 0.5-1.0 mm and is equal to the depth of the
crypts. Each villus and crypt is lined by epithelial cells that are covered with many
closely packed microvilli projecting into the intestinal lumen.
The mucosal layer is further divided into three layers: an absorptive layer (com-
posed of a continuous single sheet of columnar epithelium), the lamina propria (which
is heterogeneous in composition and cell type), and the muscularis mucosa (which sep-
arates the mucosa and submucosa).
Each villi and crypt is covered by a layer of epithelial cells having thickness of
one cell. A variety of cells are found and identified in this epithelial layer of the
small intestine. These include enterocytes, which have the function of digestion and
absorption; goblet cells, which act to secrete mucus; endocrine cells secreting hor-
mones; and M cells, which are involved in the absorption of food and antigens.
Enterocytes of the epithelial layer, more commonly known as absorptive cells, are
more commonly present on the tips of villi and mainly involved in the absorptive
function of the layer. In humans, these cells are 20-30 m in height and 8-10 m
in width. Large numbers of microvilli are present on the surface of the enterocytes.
This structure resembles a brush, and thus the microvillus border of the intestinal
epithelial absorptive cells is known as the brush border and has approximately 1.0 m
height and 0.1-0.2 m width. The cell membrane of these microvilli has a trilaminar
structure (70-90 Å thick) composed of proteins, neutral lipids, phospholipids, and
glycolipids. The plasma membrane of microvilli has an unusually high protein-lipid
ratio, owing to the presence of specialized proteins possessing enzymatic, receptor,
and transport properties.
The glycocalyx is an integral and dynamic part of the plasma membrane. This gly-
cocalyx is a uniform layer of filamentous glycoproteins [31] . The carbohydrate part
of the glycocalyx has sialic acid residues that impart negative charge to the glycoca-
lyx layer at physiological pH. The microvillus and its glycocalyx are responsible for
the digestive and absorptive functions of the enterocytes.
A variety of enzymes (peptidases) involved in the hydrolysis of peptides and pro-
teins are present in this microvillus plasma membrane. Cotransport proteins, involved
in the transport of sodium and amino acids, are found in the microvillus plasma mem-
brane. Certain substances are taken up by specific receptor proteins present on the
microvilli of enterocytes in different regions of the small intestine. For example, the
receptors for vitamin B12 complex are present in the microvilli of ileal enterocytes but
are not found on jejunal cells. This is why vitamin B12 is absorbed exclusively from
the ileum. Vitamin B12 has been explored as a delivery system for peptide and proteins
by covalently conjugating vitamin B12 to peptides (LHRH) or proteins (bovine serum
albumin, BSA) [32] .
The absorptive cell membrane rests on the lamina propria, which consists pri-
marily of connective tissue and supports the epithelium lining. Lymphoid cells and