Other Routes of Protein and Peptide Delivery: Transdermal, Topical, Uterine, and Rectal - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 646

380 mm 2 . The in utero device releases the copper mainly in the uterine fluid, partly
taken up by the endometrium, with insignificant levels in the blood. However, itching
or allergic dermatitis, possibly due to the absorption of copper from the uterus into
the circulation, was reported several months after insertion of the device. In contrast,
a recent study clearly shows that a copper IUD has no effect on gonadal, hepatic, or
renal function, or on blood copper concentrations in the Japanese monkey [152] . The
increased number of migrating cells in the endometrium was attributed to the contra-
ceptive action of the device. The risk factors for infection-related removal of an IUD
have been identified as young age, first month postinsertion, multiple sex, and high
sexual activity. Most of these risk factors are irrelevant to medicated IUD use in post-
menopausal women. It was concluded recently that the Nova-T, being widely used all
over the world, is a safe, effective, and acceptable device for contraception [153] . The
concept of using a conventional IUD as a carrier for long-term, continued intrauterine
administration of contraceptive steroids within the uterine cavity was carried over to
humans, following the observation of localized, site-specific antifertility activity of
hormones. It was shown that a progestin, released at a controlled rate from an intra-
uterine silicone capsule, was able to prevent implantation in the experimental horn of
a rabbit uterus, whereas the normal implantation proceeded in the contralateral con-
trol horn. There was no difference in plasma profiles of progesterone, estradiol, LH,
and follicle-stimulating hormone in women wearing a progesterone-releasing IUD
as compared to those using only a placebo device, indicating that the intrauterinally
administered progesterone does not have any systemic effect, but a local effect only.
The Progestasert TM IUD contains progesterone delivered at a slightly decreasing but
continuous rate (about 65 pug/day) during the 1-year lifetime of the system.
12.4 Rectal Delivery of Proteins and Peptides
12.4.1 Introduction
The rectal route of drug administration has been used for several years because drugs
are readily introduced and retained in the rectal cavity. Rectal administration may be
a practical substitute to oral administration when patients are prone to nausea, vom-
iting, convulsion, and, in particular, disturbances of consciousness. Therefore, rectal
administration has been used to deliver many kinds of drugs such as anticonvulsants,
analgesics (including narcotics), antiemetics, antibacterial agents, anesthetics for chil-
dren, some anticancer agents, and proteins and peptides. On the one hand, rectal drug
delivery is efficient because of the extensive rectal vasculature and the presence of
lymphatic vessels in the rectal region. On the other hand, patient acceptability of rec-
tal administration is much lower and drug absorption may be affected by defecation.
Peptides and proteins, a very important class of therapeutic agents, have poor oral
bioavailability due to poor absorption and easy degradation by proteolytic enzymes in
the GI tract; for therapeutic results, parenteral administration is necessary. However,
these administration routes are very poorly accepted by patients and doctors due to
allergic reaction. Thus, alternative routes such as the buccal, nasal, pulmonary, rectal,