Drug Delivery to the Cardiovascular System - Applications of Biotechnology in Cardiovascular Therapeutics - page 37

hostile environment with longer emptying time. The disadvantages are a small
absorptive area, a passive absorptive process and difficulty in ensuring that the drug
will be released at the appropriate site. The rectum offers another opportunity
where some of the disadvantages of colon can be eliminated but this route is not
popular with most patients.
Formulation of proteins/peptides with protective carriers . Although this is the most
attractive route, there are difficulties in transporting molecules across mucosal epi-
thelia and the bioavailability is still low. Oral delivery of peptides and proteins can
be carried with hydrophilic drugs dissolved in oily formulations.
Covalent addition of polymers to the protein or peptide . Protein or peptide can be
chemically changed by addition of polymers composed of water- and fat-soluble
elements.
Protein/peptide unfolding . A few companies are developing these techniques. One
of the promising technologies in this category is gastrointestinal mucoadhesive patch
system (GI-MAPS ™ ) from BioSerenTach Co Ltd, which (1) protects the drug
from the hydrolysis action of digestive enzymes by preventing the permeation
of GI fluid inside the system with water-insoluble polymer membrane and
(2) obtains high concentration gradient of both drug and absorption enhancer on the
intestinal mucosal surface by adhering to the target site of the intestine. After oral
administration of gelatin capsule containing GI-MAPS, drugs in the formulation are
protected from the gastric juice in the stomach by enteric film on the adhesive layer
(adhesion site-controlling layer) and protection layer. When GI-MAPS is transferred
to the small intestine, the adhesion site-controlling layer of GI-MAPS is dissolved
at the target site of the small intestine, and then GI-MAPS adhere to the intestinal
mucosal membrane. As a result of adhesion, the drug carrying layer of GI-MAPS
existing between protecting layer and adhesive layer forms a closed space. Drug in
the closed space is protected from the attack of the digestive enzymes in the intestinal
lumen. When drug in the drug carrying layer is dissolved by intestinal fluid, high
concentration of drug solution can be obtained. As a result of high concentration
gradient of drug between the system and the enterocytes, formulated drug can be
efficiently absorbed. In addition, when an absorption enhancer coexists with a drug
in the drug carrying layer, the concentration of enhancer as well as drug in this
closed space reaches to high degree. Under this condition, optimal absorption
enhancing effect can be obtained. This technology can be applied for the delivery of
interferon, insulin, calcitonin, granulocyte colony-stimulating factor (G-CSF),
epoietin, growth hormone, interleukins, desmopressin, etc.
Peptide transporters . PEPT1 and PEPT2 play an important role in the maintenance
of protein nutrition and in the handling of endogenously derived peptides. These
transporters also have significant pharmacological and pharmacokinetic relevance
to the transport of various peptide-like drugs.
Fusion with transferrin . Transferrin is a plasma protein found in blood. Humans
naturally produce transferrin to move iron through the blood to the liver, spleen,