Oral Delivery of Proteins and Peptides: Concepts and Applications - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 506

Some dual-acting excipients are also used to obtain a synergistic effect on the
total amount of drug transported. An example is bile salts, which act as penetra-
tion enhancers and also as protease inhibitors, thus augmenting oral absorption. The
mechanism behind its use as a protease inhibitor is inhibition of the membrane and
cytosolic proteases [186] . Studies supported that a significant hypoglycemic effect
was obtained following large intestinal administration of insulin with 20 mM sodium
glycocholate, camostat mesilate, and bacitracin [187] .
Researchers have also proposed the use of biodegradable and mucoadhesive poly-
mers to encapsulate proteins in a particulate system and then attach the protease inhibi-
tors covalently onto the surface of the particles. When such a system is given orally,
particles adhere to the membrane and release the protein for its absorption through
mucosa. Here, protease inhibitors create a microenvironment that is free from enzy-
matic activity and thus act locally without affecting the activity of digestive enzymes.
In another study, hydrogel beads have been developed containing enzyme inhibitor
(ovomucoid or soyabean trypsin) covalently coupled on the polymeric material [188] .

10.6.7 Specialized Drug Delivery Systems
10.6.7.1 Liposomes
Nowadays, liposomes have gained much more attention for their entrapment of pep-
tides to improve stability and for their effective delivery. They entrap both lipophilic
and hydrophilic drugs and thus are useful for a wide variety of bioactives. The main
disadvantages of liposomal delivery of peptides include limited stability of liposomes
and degradation of proteins during the formulation of proteins due to the use of organic
solvents [189] . Efforts are continuously made to stabilize liposomes by formulating
polymerized liposomes, which are stable even in the brutal environment present in the
stomach and intestine. Liposomes are a useful tool for delivering peptides to the sur-
face of mucosa, which in turn are useful in localizing a greater amount of the drug
in the membrane. Researchers studied another approach where protease inhibitors are
also being incorporated in the formulation to improve the performance of less effective
liposomal peptide delivery systems; for example, aprotinin is incorporated into Factor
VIII-loaded liposomes, made up of lecithin and phosphatidic acid [65] .
Liposomes are also taken up by Peyer's patches and thus increase the uptake of
any entrapped drug. Negatively charged liposomes containing at least 25 mol% phos-
phatidylserine have been reported to be taken up readily by the rat Peyer's patches
following intraluminal administration [190] .

10.6.7.2 Microemulsions
Microemulsions may be used as the carrier for protein and peptide delivery to the GI
tract. With all types of microemulsions, water-oil-water type microemulsion offers
unique advantages, including these:

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Degradation of proteins is effectively reduced due to the use of relatively mild conditions
during the formulation process of microemulsions.