Biomedical Engineering Reference
In-Depth Information
Table 10.3 Oral Absorption of Peptide and Proteins in Relation to Molecular Weight
Peptides and Proteins
MW
Amount of
Absorption (%)
References
Dietary di- and tripeptides
200-300
5-50
82
Dietary tetrapeptides
400
5
83
Thyrotropin-releasing hormone
(TRH) analogs
400
5
83
Enkephalins
600
2
83
Cyclic somatostatin
806
5
83
Bradykinin
1060
2
83
Vasopressin
1200
2
83
Cyclosporine
1203
50
84
Leuprolide
1208
5
85
Beta-endorphin
3500
2
83
Calcitonin
3500
2
83
Corticotropin (ACTH)
4700
2
83
Insulin
5700
0.5
85
Growth hormone
22,600
2
83
Horseradish peroxidase (HRP)
40,000
3
86
Bovine serum albumin (BSA)
50,000
4.5
87
peptide chain may be even more important than the value of the partition coeffi-
cient in the prediction of oral permeability. The change in pH of medium results in
a change in charge density and degree of ionization, and thus permeability of the
peptides [94] . At physiological pH or at a pH above the isoelectric point (p I ), the
epithelial proteins are negatively charged and are selective to positively charged sol-
utes, and vice versa [95] . At the isoelectric point, the membrane is nondiscriminat-
ing to either ion [96] . This phenomenon has a significant effect on the absorption of
proteins and peptides and helps the formulator to design the composition. Due to the
negative charge of insulin, it was found to be excluded from the aqueous paracellular
pathway, whereas positively charged peptides, such as thyrotropin-releasing hormone
(TRH), were taken up predominantly via this pathway [95] .
10.5.4  Solubility, Lipophilicity, and the Partition Coefficient
Because of their amphoteric nature, the pH-dependent solubility profile is not uni-
form for all peptides. At the isoelectric point, proteins exist in a zwitterion state and
have minimum water solubility. Solubility is also dependent upon pH, metallic ions,
ionic strength, and temperature. Proteins and peptides are usually water soluble and
have a much smaller oil-water partition coefficient. The solubility of proteins can be
reduced by blocking the C-terminal through cyclization, amide formation, or esterifi-
cation [78,97-101] ( Table 10.4 ).
These modifications have been utilized to increase lipophilicity of proteins and thus
their absorption by the passive diffusion pathway. Although the octanol-water partition
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