Oral Delivery of Proteins and Peptides: Concepts and Applications - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 512

10.7.2 In Vivo Studies
In vivo animal studies are generally carried out to check the dissolution profile of dos-
age form, rate and extent of drug absorption, and stability of the drug and dosage form.
These studies reduce the cost of development by reducing the number of failed clinical
trials. Various animal models are used for such studies, and selection of animal model
depends on drug, dosage form, indication, and type of study. But generally these pre-
clinical in vivo studies are performed in dogs. Before doing such studies, metabolic
and physiological differences between selected animal model and humans must be well
characterized for such studies to be useful. Gastrointestinal motility affects the rate and
extent of drug absorption, and thus drug absorption in the anesthetized animal is dif-
ferent from the conscious animal. A study characterizing the upper GI pH, volumetric
flow rate, and the activity of chymotrypsin in mongrel fistulated dogs as a function of
fasted, GI motility phase has been reported [225] . The anatomical site where a peptide
is released from its formulation prior to its absorption is determined by radioiodination
of peptide in conjunction with -scintigraphy. The regional perfusion technique is gen-
erally used when the in vivo approach is applied in humans [226] . A multichannel per-
fusion tube is introduced orally, which has two inflatable balloons 10 cm apart from
each other. Thus a segment of 10 cm length can be perfused without contamination of
luminal contents from proximal and distal segments [227] .
10.8 Strategic Use of Oral Route for Immunization
Generally, vaccines are administered through the parenteral route. But the site of entry
of most bacteria and viruses is mucosa. So better protection can be offered when a vac-
cine is given through the mucosa, where bacteria enter the body. Currently, only few
oral vaccines are available, so this field of oral immunization should be exploited to a
large extent to develop more oral vaccine for better patient compliance. Oral immuni-
zation has another advantage, that of self-immunization, where the patient alone can
administer a vaccine, without a healthcare professional; this is the case in countries
where healthcare professionals are present in much fewer numbers [228,229] .
The presence of M cells in Peyer's patches makes oral immunization more advan-
tageous. Antigens of the given vaccine are captured by M cells and transported to the
lymphatic system. After gaining entry to the lymphatic system, antigens spread to
different sites and produce immune response at multiple sites. Generally, the intes-
tinal segment is considered to be a immunologically nonresponsive environment
because it produces a poor response to food and environmental antigens. Thus, it is
very difficult for an orally given antigen to produce an immune response in such a
nonresponsive environment. The intestinal segment also acquires tolerance to fre-
quently given antigen.
Relatively safe bacteria or viruses, erythrocytes, liposomes, and micro- or nanopar-
ticles are used to target the antigen to inductive sites [228] . For this purpose, the size
of such carriers should be in a range of 5-10 m to stimulate a mucosal response.
Potent oral adjuvants, such as cholera toxin, have been tried for the induction