Other Routes of Protein and Peptide Delivery: Transdermal, Topical, Uterine, and Rectal - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 643

Use of iontophoresis and phonophoresis to achieve topical delivery may be extended
to peptide and protein drugs. In fact, as discussed, insulin forms a depot or reser-
voir in the skin on iontophoretic or phonophoretic delivery. Although this may not
be a good scenario for drugs delivered for systemic effects, depot formation may be
advantageous for certain topical drugs.
12.3 Intrauterine Delivery of Proteins and Peptides
12.3.1 Introduction
Generally, high-molecular-weight drugs, and peptides and proteins in particular, are
usually delivered by parenteral route because they are either degraded in the GI tract
or poorly absorbed. Repeated injections are often required because of the drug's short
half-life and the chronic nature of many diseases. To optimize therapy, it is essential to
search for a nonparenteral route of drug administration. Intrauterine drug delivery has
been proposed as a new route of drug administration relatively recently. Two polypep-
tides, calcitonin and insulin, were reported to be absorbed from the uterus of the rat
in a biologically active form [144,145] . The extent and duration of hypocalcemic and
hypoglycemic effects induced by intrauterine delivery of calcitonin and insulin, respec-
tively, were measured and were equivalent to those obtained after subcutaneous injec-
tions. The role of cervical mucus in drug delivery via the vagina and cervix has been
reviewed [146] . The viability and integrity of the mucosal tissue must be monitored
during in vitro studies, such as those done in using chambers [147] . Only very few stud-
ies have evaluated this route thus far, and more work is likely to appear in the future.
12.3.2 Drug Absorption Through the Intrauterine Route
A number of drug substances are known to act directly upon the uterus, including
uterine relaxants (e.g., -agonists) and stimulants (e.g., prostanoids, oxytocin). The
administration of drugs to the uterus is achieved by the application of a formulated
product to the vagina or the cervix. But it has been demonstrated that the mechanism
by which the drug is transported from the cervicovagina to the uterus is not limited
to passive diffusion, but is facilitated by a preferential transport mechanism termed
the first uterine pass effect.
As shown in Fig. 12.7 , the uterus in a human is a pear-shaped, thick, muscular
organ composed of three major anatomical divisions—corpus, isthmus, and cervix.
The main uterine cavity comprises the upper two-thirds of the uterus and is known
as the corpus. It is several centimeters in diameter and connected on both sides to the
fallopian tubes. Below the corpus, the uterus narrows to form the isthmus, which ter-
minates, through the cervical canal, in a constricted opening into the vagina known
as the cervix. The main functions of the uterus include transportation of sperm from
vagina to uterine tubes for fertilization; site for implantation, nourishment, and pro-
tection of embryo and fetus; expulsion of the fetus at term, through the vagina to
outside, by powerful contractions of its thick muscular walls.