Other Routes of Protein and Peptide Delivery: Transdermal, Topical, Uterine, and Rectal - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 650

tetra-acetic acid (EDTA) may improve the in vitro rectal penetration of insulin in the
albino rabbit. [178] . The absorption-promoting effect of sodium 5-methoxysalicylate
was also observed in the rat with respect to rectal delivery of pentagastrin and gastrin
[174] . Rectal bioavailability was quantified by direct comparison of pharmacological
effect with intravenous dose response. Rectal absorption of des-enkephalin--endor-
phin (DE--E) was enhanced by medium-chain glycerides and EDTA in conscious
rats [179] . Coadministration of the absorption adjuvant greatly enhanced the rectal
bioavailability of the model peptides [180] . Enamine derivatives of phenylglycine
are also studied as an adjuvant for the rectal absorption of insulin [181] . Enamine
derivatives have been shown to increase support absorption of insulin in the dog and
rabbit [181-184] . Recently, the effect of various absorption enhancers was examined
on the transport of insulin across the rectal membrane of albino rabbits by in vitro
using the chamber method. Insulin could not cross the rectal mucosa without absorp-
tion enhancers, but its transport was improved in the presence of various absorption
enhancers. Among absorption enhancers, Na-glycocholate (Na-GC) was more effec-
tive than Na-taurocholate (Na-TC), but less effective than Na-deoxycholate (Na-DC)
and polyoxyethylene-9-lauryl ether (BL-9) in enhancing rectal transport of insu-
lin [185] . The transport of YAGFM (D-Ala2 Met enkephalinamide) [119] was also
enhanced by the addition of 1% Na-GC. Increasing the Na-GC concentrations further
increased rectal insulin transport. Although EDTA at 0.01% and 0.1% did not affect
rectal transport of insulin, it augmented the penetration enhancement effect of 1% Na-
GC. Uchiyama et al. examined the transport of insulin across the colonic membranes
in vitro using the chamber method in the presence of various absorption enhancers
[173] . Insulin transport was enhanced by the addition of Na-DC, EDTA, n -lauryl-
P-D-maltopyranoside (LM), and Na-caprate (Na-Cap), although other enhancers did
not improve its transport across the colonic membrane. Insulin suppositories in rabbits
are also studied [186] , and rectal insulin suppositories have been studied for hypogly-
cemic effect [187] . Various nonsteroidal antiinflammatory drugs (NSAIDs) have been
studied for effect of drug absorption through the rectal mucosa [188,189] . Salicylate
and other enhancers were found to increase rectal absorption of erythropoietin in rats
[190] . In the same way, rectal bioavailability was shown to be enhanced by sodium
5-ethoxysalicylate [174] . Enhanced absorption was also shown by nonsurfactant adju-
vants in rats [191] and by salicylates [192] for insulin, heparin, and dextran in rats.
Thus, some of the absorption enhancers were effective for improving the absorption
of insulin [193,194] ( Table 12.2 ).
12.4.4.1.2 Various Absorption Enhancers for the Rectal Route
In this section, we describe those factors that regulate the effectiveness of various
absorption enhancers.
Cyclodextrins Cyclodextrins are known to alter various properties of drugs, phar-
maceutical formulations, and biomembranes, resulting in enhancement and modula-
tion of rectal drug absorption. Cyclodextrins, cyclic oligosaccharides consisting of
several glucopyranose units, are host molecules, which form inclusion complexes.
Hydrophobic cyclodextrins derivatives may modulate the release of drugs from the