Proteomics - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 395

U.S. Patent 2006997863B2 [31] describes a delivery system composed of a mag-
netic particle attached to a target-specific ligand, which, when administered to a
patient by applying a magnetic field, triggers the drug release. This technology can
be harnessed in designing target-specific drug delivery in cancer therapeutics.
Advances in the field of novel drug delivery systems have also provided a huge impe-
tus to pulsatile or triggered-release drug delivery systems. Being biocompatible, stable,
and capable of controlling the release profile of bioactives, these systems are potentially
useful for delivery of labile and challenging molecules like proteins, peptides, hormones,
and various endogeneous substances, as well as in achieving targeted drug delivery in
cancer therapeutics. The system also seems to be promising for enhancing the safety,
efficacy, and stability aspects of existing medicines. The major drawbacks in these poly-
mer-based triggered-release systems arise from biological variations among individuals.
Medical and pharmaceutical scientists should now focus on the importance of the trig-
gered release of drugs. The key considerations in the design of these systems are their
biocompatibility, the toxicity of polymer-based devices, response to external stimuli, abi-
lity to maintain the desired levels of drugs in serum, shelf life, and reproducibility.
8.3.5 On-Demand Release Systems
As the name indicates, these systems are capable of delivering drugs as and when
needed. The principle underlying the working of these systems is primarily the appli-
cation of an external magnetic field to release the drug from a system that has been
implanted in the body.
8.4 Barriers to Protein and Peptide Absorption in the
Gastrointestinal Tract
A major limitation of protein drug delivery is rapid inactivation of proteins by proteo-
lytic enzymes in the gastrointestinal tract following oral administration. Degradation
of proteins occurs by varied mechanisms: (1) hydrolytic cleavage by proteases,
(2) chemical modification like oxidation, phosphorylation, to name a few. These
chemical changes lead to inactivation of the protein and thereby loss of physiological
or pharmacological activity. Hence, a major challenge in peptide drug delivery is to
overcome or circumvent the enzymatic barriers. Many times, degradation begins at
the site of administration itself. For instance, subcutaneous or intramuscular bioavail-
ability of proteins is much less than expected. Proteases are one of the major classes
of enzymes that catalyze a number of degradation reactions. The majority of these
proteases are synthesized as inactive precursors called zymogens, which get activated
at the site of action, under the influence of some endogeneous chemical.
8.4.1 Digestive System
The digestive system originates from the mouth and ends in the rectum. The entire
digestive system is also referred to as the alimentary canal, which is divided into