Proteomics - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 399

Nucleus

Transmembrane channel

Tight junctions

Vesicle

Fenestra diaphragm

Figure 8.2 Schematic view of vascular endothelium—one of the barriers in protein
absorption.

as in distribution from the site of action, administration, and absorption. In spite of
relentless efforts, vascular endothelium ( Fig. 8.2 ) has been an insurmountable bar-
rier to formulation chemists and experts of drug delivery systems. The problem is
further complicated in the case of proteins and peptides. Rational drug design sup-
ported with a deep understanding of anatomical, structural, and physiological fea-
tures of these membranes may in the future facilitate meaningful protein delivery.

8.4.3.1 Intestinal Epithelial Barrier
�.4.�.1.1 Organization and Architecture of the Small �ntestinal Mucosa
In an average adult human, the small intestine is approximately 280 cm long and 4 cm
in diameter. A schematic view of the intestinal epithelial cells is shown in Fig. 8.3 .
The structural characters effectively increase the surface area for drug delivery. In
a normal, healthy adult human, the small intestine exhibits three anatomical modifi-
cations that drastically increase their surface area. Those modifications are:

1. Plicae circulars or folds of Kerckring: They are spiral shaped, concentric folds and are
1 cm high as well as 5 cm long. The number of these folds is highly variable throughout the
small intestine with their maximal distribution in distal parts of duodenum and proximal
part of jejunum.
2. Superimposed on these folds as well as present in the interstitial spaces of these folds are
tiny sized, hairy projections called villi, spread throughout the small intestine. However,
their number, shape and density are varying in the different parts of small intestine.
3. The surface of this villus exhibits the presence of columnar epithelial (absorptive in nature)
and some flask shaped goblet cells. There are projections of microvilli on the apical ends
of absorptive cells and are more commonly referred to as brush border.
The mucosa of the small intestine consists of three main layers: the muscularis mucosa,
the lamina propria, and the epithelial cells. The muscularis mucosa is a continuous
sheet of smooth muscle lying between the mucosa and submucosa. Numerous defen-
sive cells, such as lymphocytes, plasma cells, and macrophages, are found here.

�.4.�.1.2 Absorptive (Villus) Cells
The absorptive cells of the small intestine are columnar cells, whose major function
is absorption.