Oral Delivery of Proteins and Peptides: Concepts and Applications - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 507

l Use of protein-compatible ingredients such as surfactants, water, and oils. These excipients
are used in pharmaceutical formulations and generally recognized as safe. Their toxicities
and metabolic profiles are well-known.
l Microemulsions are stable for relatively long periods. Microemulsions are recognized as a
thermodynamically stable system.
l Microemulsion-based formulations are prepared in liquid forms, which are preferable for
patients with difficulties in swallowing solids.
Along with the stability of proteins, the stability of the microemulsion is also
important for effective delivery to the GI tract [191-193] . The composition of the
microemulsion greatly affects the stability of the microemulsion in the GI tract.
Penetration enhancer and protease inhibitors may also be incorporated in microemul-
sion composition to improve the delivery of peptides to the GI tract [191] .
10.6.7.3 Micro- and Nanoparticles
Various materials including gel-forming polymers, pH-dependent polymers, and site-
specific biodegradable polymers may be used to develop beads, microspheres, and
nanoparticles for effective oral delivery of proteins and peptides. Among them, gel-
forming, polymer-based formulations are extensively studied for their protein encap-
sulation and release of the bioactive. pH-dependent polymers are also used to protect
the peptides from the acidic environment present in the stomach by tailoring the release
from the micro- and nanoparticles. These polymers prevent the release of peptides in
the acidic environment and hence increase the amount of peptide available for absorp-
tion. Biodegradable microparticles protect the peptide in the stomach and then gradually
release them in intestine. Hydrogel-forming polymers are modified to get the material,
which is only degraded by colonic microflora. Such a system releases the peptides in the
colon where the pH is nearly neutral and proteolytic enzyme activity is very low.
The stability of some proteins and peptides after oral administration is also
increased by encapsulating them in albumin [194] . In situ microparticle formation
occurs when proteinoids come in contact with the acidic environment after oral
administration. There are reports suggesting effective delivery of calcitonin encap-
sulated in proteinoid microspheres to rats and monkeys [195] . Poly(d,l-lactide- co -
glycolide) nanoparticles fail to deliver the drug after oral administration because they
significantly accumulate the drug in the liver and have a short GI transit time [196] .
Peyer's patches are mainly responsible for the absorption of nanoparticles, espe-
cially in the ileum after oral administration, whereas in the jejunum nanoparticles
may be absorbed by the paracellular pathway. Nanoparticles may pass through the
intercellular spaces formed by the desquamation of well-differentiated absorptive
cells at the tip of the villi [197] .
It has been concluded from the study that insulin-loaded polyalkylcyanoacrylate
nanocapsules when administered to diabetic rats show significant reduction in the
glycemia up to 50-60%. Hypoglycemic effect starts at day 2 and the effect persists
even after 20 days [198] . The results are very superior to plain insulin delivery [199] .
Sustained drug release has also been achieved from polyisobutylcyanoacrylate
nanoparticles loaded with insulin and calcitonin. Initial absorption was less due to