Oral Delivery of Proteins and Peptides: Concepts and Applications - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 509

contain a hydrophobic core and encapsulate hydrophobic drugs. Polyion complex
micelles entrap biomacromolecules such as enzymes and DNA, and may attain increased
stability against various environmental factors [208] . Encouraging results have been
obtained by researchers in the oral delivery of polymeric micelles, because they cross the
intestinal barrier after oral administration [209] . Thus oral delivery of macromolecules,
that is, peptides and proteins, is also possible by means of polymeric micelles.
10.7 Technique for Oral Absorption Studies
Newly synthesized peptides and proteins and their delivery systems may be evaluated
for both in vitro and in vivo release and mucosal permeation by designing appropri-
ate experiments.
10.7.1 In Vitro Studies
10.7.1.1 Diffusion Cells
Various types of diffusion cells are used to evaluate the transepithelial transport and
metabolism of several compounds. The Frans diffusion cell and the Ussing chamber
are the most widely used diffusion apparatuses for these purposes. Here intestinal
segment is used as a semipermeable membrane that separates the donor and acceptor
compartment [210] . Reduced leakage, better mixing, increased working tissue sur-
face area, and easier cleaning are added features of modified diffusion cells. Certain
modifications have also been made to maintain constant temperature of the donor
and acceptor compartment throughout. Today there are novel systems which mea-
sures electrophysiologic changes in the cell, such as transepithelial electrical resis-
tance (TEER), which is a useful index of tissue integrity and viability [211] .
10.7.1.2 Intestinal Segments
In vitro studies or ex vivo perfusion studies are performed using an isolated segment
of intestine. Segments from various sites are isolated and perfused according to the
need. An everted gut sac apparatus has been used to study site-specific absorption of
insulin from various intestinal regions of the rat. Everted gut sac apparatus is named
so because here the intestinal segments are everted on a thin stainless steel rod and
ligated on the other end with a silk thread. The sac created by tying one end of seg-
ment is filled with a known volume of modified Kreb's ringer phosphate bicarbonate
buffer and placed inside a test tube containing the test solution at 37 o C, which was
continuously bubbled with 95% O 2 /5% CO 2 to provide the physiological condition.
A definite amount of load was also applied to the everted sac to prevent peristaltic
muscular contractions. At time intervals, samples are withdrawn from both serosal
and mucosal compartments and analyzed for the amount of drug absorbed.
Even though physiological conditions are maintained, the isolated segment is only
viable for 20 min and a maximum of up to 3 h in some cases. The short viable time is