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12
MARCH 2011 • TransDermal
On the Transdermal Formulation of Peptide
and Protein Drugs
Xiaorong Shen and David Jones, Primera Analytical Solutions
This short review covers some of the recent
approaches to transdermal formulations for
delivering proteins and peptides. These methods
may overcome some of the difficulties
associated with the delivery of those molecules.
Protein and peptide drugs offer powerful therapeutic
benefits to patients. While companies
have marketed them since the introduction
of insulin in the early twentieth century, the methods
for dosing patients usually have been limited
to administration by injection. This method not only
is inconvenient for patients but also causes other
difficulties, such as allergic reactions at the injection
site. For drugs with relatively short half lives, injection
methods — without the use of IV solutions —
do not afford maintenance of appropriate levels of
the drug without repeated dosing. The most convenient
type of dosing, oral, is generally not available
for peptide and protein drugs because proteolytic
enzymes in the alimentary canal hydrolyze the
peptides.
Peptides are widely used in skin-care products,
mostly in connection with the cosmetics industry,
although medical providers routinely apply antibiotic
peptides, such as polymyxin B, topically for
wound care and other dermatological infections.
While such topical use is important, the ability to
transport peptides and proteins into physiological
matrices in other organs is of vital importance.
Proteins incorporate four levels of structure:
• A primary structure that derives from the aminoacid
sequence
• A secondary structure that arrangements in
helices and sheets define
• A tertiary structure that refers to the way that the
secondary structures fit together as a whole
• A quaternary structure that is a representation of
protein-to-protein interactions; for instance, whether
the proteins are monomers, dimers, or oligomers of
single or multiple protein units.
Effects of Structure
All of these structures affect not only the transport of
these molecules but also their activity. To a lesser
extent, the problems with hydrolysis, absorption,
and stability also apply to peptides that, while
smaller, exhibit at least a primary and a secondary
structure. Both proteins and peptides also often
depend on intramolecular bonds that can rearrange
under some circumstances. Most often disulfide
linkages connect these bonds, but some peptides
are cyclic in nature. Again polymixin B is an example.
Any chemical exposure can affect molecular
rearrangement, racemization, and rearrangement of
disulfide bonds, further complicating attempts to
formulate and deliver them.
Nevertheless many approaches to transdermal
formulation are now under active investigation,
and some have reached the stage of clinical
development.
Approaches to Transdermal
Formulation
The dermis is the vascularized portion of the skin
where hair follicles originate, where lymph vessels
and sweat glands are found, and where drugs can