This article is part of a special issue on Drug Delivery
The benefits and drawbacks associated with traditional transdermal delivery are well known. Transdermal delivery is popular
with patients; it is comfortable, convenient to use and non-intimidating. Unfortunately, passive transdermal patches are compatible
with a relatively small number of drugs, all of which are small molecules and of low water solubility. Recent advances in
the development of new transdermal delivery options seek to maintain the features of transdermal delivery that patients appreciate
while increasing the number of compounds that can be delivered. Two of the fastest growing segments of the pharmaceutical
market, vaccines and therapeutic proteins, have been targeted for transdermal delivery, and there may be therapeutic advantages
associated with the transdermal delivery route for both.
Structurally and physiologically, the skin is an important part of the immune system, providing front-line defense against
various environmental assaults. In particular, mammalian skin is a dynamic barrier that exists in a variety of densities,
textures, and layers to negotiate external stimuli. The uppermost layer of the skin, the epidermis, is capped by the stratum
corneum, a layer of flat, plate-like cells known as keratinocytes. These cells prevent dehydration and provide a physical
and chemical barrier to the outside world, protecting underlying tissues from particulates, bacteria, and viruses. Overcoming
the barrier properties of the stratum corneum has, historically, provided one of the most significant challenges to transdermal
delivery of water-soluble compounds such as proteins, peptides, and vaccines. The epidermis, which lacks a microcirculatory
structure, varies in thickness from approximately 20–100 µm (1–3).
The dermis, which lies beneath the epidermis, is sometimes characterized as having an upper section (the papillary dermis)
and a lower section (the reticular dermis); altogether, the dermis is about 1.5–3 mm thick (1, 4). The dermis contains a network
of collagen fibers as well as an upper and lower plexus of both blood vessels and lymph vessels. The dermis, in general, and
the upper portion of the dermis, in particular, has the highest density of lymphatic capillaries in the body (3, 5–7). The
dermis is the major site of fluid exchange between the blood, lymphatic capillaries and interstitial fluid (2). 
