Other Routes of Protein and Peptide Delivery: Transdermal, Topical, Uterine, and Rectal - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 637

terms of ion-exchanger capacity for removal of that particular ion from a solution.
Novel applications of ion-exchange materials include enhancement of drug release
and increasing the dissolution rate of the poorly soluble drugs. Ion-exchange materi-
als used for medical and pharmaceutical applications are usually in a form of fibers
[94-99] , membranes [100] , and resins [101] . The equilibrium reaction between the
ion-exchange device and a particular organic ion of significant molecular weight
of typical drugs is controlled by the environment in which the drug and the ion-
exchange material are found.
Factors controlling the equilibrium constant include molecular weight, p K a of drug
and resin, pH of the solvent, ionic strength, hydrophobicity and hydrophilicity, and
concentration of competing ions. Drug ions, which are attached to the ion-exchange
materials via electrostatic interactions, provide a more accurate and homogeneous
control of the ion-exchange process so that drug release rate can be easily adjusted.
Ion-exchange fibers could be a good material to successfully store an easily degrad-
able drug. Drug stability was greatly enhanced by attaching drug to ion-exchange
fibers in an acidic or basic environment. Drug ions attached to the ion-exchange mate-
rials through electrostatic interactions provide a more precise and uniform control of
the ion-exchange process, so the drug release rate can be simply adjusted [97,98] .
A combination of iontophoresis with electroporation, chemical enhancers, sono-
phoresis, microneedle, and ion-exchange material may provide easier and more
accurate delivery of macromolecules and poorly water-soluble compounds. The skin
irritation associated with iontophoresis has been addressed by several studies and is
an issue preventing wide application of the technology [12] . Nevertheless, the blend
with other enhancement techniques may result in the need for less strong current to
reach therapeutically effective delivery amounts, and hence will considerably reduce
the skin irritation problem.
12.1.4.2 Chemical Approach
Application of peptides and proteins as clinically useful drugs is a major challenge.
This is due to their poor delivery characteristics caused by their metabolic instability
and general hydrophilic character, resulting in poor transport across biomembrane.
This typically leads to bioavailability less than 1-2%. Once within the systemic cir-
culation, a short biological half-life is normally observed due to rapid metabolism
and clearance from the body. A possible approach to solve these delivery problems
could be chemical amendment or derivatization.
Two approaches may be possible:
1. Permanent chemical change in the drug molecule (also referred as the analogue approach).
2. Bioreversible derivatization of the bioactive peptide or protein (also referred as the prodrug
approach).
Normally, analogues are not bioreversible. Both the prodrug and the analogue
should have better absorption and/or stability characteristics over the parent drug
molecule. The analogue should also have high receptor selectivity and affinity. In the
literature, different terms such as analogues and peptidomimetics find use to describe