ABSTRACT
Acknowledgments .............................................................................................................. 348
References .......................................................................................................................... 349
The skin represents an attractive gateway for the localized and systemic delivery of therapeut-
ically active molecules due to its ready accessibility, avoidance of gastrointestinal degradation
and liver inactivation, monitoring capability and potential for improved patient compliance.
The ability to deliver therapeutic quantities of medicaments to and through the skin, however,
is dependent on the physicochemical properties of the candidate drug and the significant barrier
properties of the target tissue. After all, a primary function of the skin is to restrict the ingress of
external matter through physical blockade and immune surveillance. Whereas traditional
transdermal delivery techniques use formulation strategies to promote the transport of small
molecules through the stratum corneum, a growing number of delivery techniques that aim to
bypass or disrupt the skin barrier have been developed. Such strategies, including the use of
chemical enhancers [1], iontophoresis [2], electroporation [3], and sonophoresis [4] may sup-
plement traditional transdermal delivery strategies or provide a means of delivery for new drug
candidates, including macromolecules. Despite these advances, and a few exceptions, it could
be argued that effective transdermal delivery is still generally restricted to a small number of low
molecular weight, weakly lipophilic, and potent therapeutic molecules. Increasing emphasis on
the administration of biotechnology-derived macromolecular, particulate-and DNA-based
medicines requires the development of further delivery strategies and devices that circumnavi-
gate the stratum corneum barrier to promote delivery of a wide range of therapeutics to the
underlying epidermis, dermis, and possibly the systemic circulation. Clearly, as the requirement
for the efficient delivery of larger molecules and nanoparticles increases more radical methods
of disrupting skin barrier function are required.
