Oral Delivery of Proteins and Peptides: Concepts and Applications - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 491

Table 10.4 Lipophilicity of Some Peptides

Peptide Partition Coefficient ( n -Octanol/

Buffer, pH 7.4)

Insulin 0.0215

Luteinizing hormone-releasing hormone 0.0451

Thyrotropin-releasing hormone 0.0376

Glucagon 0.0633

Substance P 0.275

Met-enkephalin 0.0305

Leu-enkephalin 1.12

Ref. [80] . (Reprinted with permission from Elsevier)

coefficient is a simple parameter that may predict mucosal permeability, its correlation
with absorption of peptides is not always observed, as the oral bioavailability of pep-
tides models varies parabolically with their lipophilicity [78,102] ( Table 10.4 ).
Absorption of drugs through oral route follows the pH-partition hypothesis,
which implies a passive diffusion mechanism [103,104] , where the absorption rate
is directly proportional to the concentration of drug molecules in the unionized form.
Drug absorption decreases with increase in extent of ionization.

10.5.5 Aggregation
Aggregation self-association and hydrogen bonding affects the intrinsic properties of
peptides. Insulin has a tendency toward aggregation that is accelerated in the pres-
ence of ionic ingredients and phenolic preservatives. Complexation of insulin with
zinc prevents aggregation and makes it more stable [105-107] . Nonionic surfactants,
such as Pluronic F68, are used for stabilization of insulin [108] .
Some peptides have a tendency to form a hydrogen bond with water molecules.
This leads to the addition of a hydroxyl group and thus a decrease in partition coeffi-
cient and the ability to penetrate a lipidic membrane, therefore resulting in a decrease
in permeability [78,79,107,109-113] . However, hydrogen bonding sometimes leads
to increased permeability. Hydrogen bonding among protein molecules results in
the formation of a cyclic structure, which decreases hydrogen bonding with water,
increases lipophilicity, and thus increases permeability [114-116] .

10.6 Approaches to Improve Oral Protein and Peptide
Delivery

10.6.1 Targeted Delivery of Peptides and Proteins
Different regions of the GI tract have different specificity for different peptides and pro-
teins; thus their absorption dose is not the same throughout the GI tract. It is concluded