Other Routes of Protein and Peptide Delivery: Transdermal, Topical, Uterine, and Rectal - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 649

12.4.4 Approaches to Improve Rectal Absorption of
Proteins and Peptides
12.4.4.1 Absorption Enhancers
Extensive studies have been conducted related to rectal absorption of peptides and
proteins. Nevertheless, in the absence of an absorption-promoting adjuvant, the rec-
tal absorption of these drugs is much less than for intramuscular, intravenous, or sub-
cutaneous administration. Incomplete absorption is probably due to a combination of
poor membrane permeability and metabolism at the absorption site. Thus, a number
of absorption enhancers have been utilized for improving rectal absorption of larger
polypeptides and proteins. Examples of various peptides and proteins delivered
through the rectal route along with their respective absorption enhancers are listed
in Table 12.1 . Many absorption enhancers were utilized to enhance the absorption of
rebamipide [171] , insulin [172,173] , polypeptide [174] , heparin [175] , and interferon
[166] . These absorption enhancers were adopted not only for the GI tract but also for
other alternative routes such as nasal, buccal, ocular, pulmonary, vaginal, and rec-
tal routes. There are many factors affecting the effectiveness of absorption enhanc-
ers such as the physicochemical characteristics of the drugs, administration site, and
species differences.

12.4.4.1.1 Absorption Enhancers and Their Mechanism
Among the peptides and proteins, insulin is probably the most frequently studied pro-
tein with respect to rectal absorption. Nishihata et al. examined the effect of salicy-
lates on rectal absorption of insulin in dogs [172] . The absorption-promoting effect of
sodium deoxycholic acid, sodium taurocholate, polycarbophil, and their combinations
were also studied in diabetic rabbits with respect to rectal insulin suppositories [176] .
It was found that sodium salicylate and 5-methoxysalicylate both increase the rectal
absorption of insulin [174,177] . It was also found that bile salts and ethylenediamine

Table 12.1 Absorption Enhancer for Different Proteins and Peptides

Protein or Peptide Enhancer Reference

Human chorionic
gonadotropin

-Cyclodextrin [170]

Insulin Nitric oxide donor S -nitroso- N -acetyl-D,L-

penicillamine (SNAP)

[167]

()-(E)-4-methyl-2-[(E)-hydroxyimino]-5-nitro-6-
methoxy-3-hexenamide (NOR1)

[173]

()- N -[(E)-4-ethyl-2-[(Z)-hydroxyimino]-5-nitro-
hexen-1-yl]3-pyridine carboxamide (NOR4)
Docosahexaenoic acid

[168]

Sodium laurate and acrylic hydrogel [169]

Polypeptides 5-Methoxysalicylate [174]

Rebamipide Sodium laurate and taurine [171]