Transdermal drug delivery

Abstract

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin's barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase its impact on medicine.

Figure 1

Cumulative number of transdermal drugs approved by the FDA since the first approval in 1979. There are currently 19 drugs and drug combinations administered by various delivery methods that are approved in the United States (see Table 1). Data were obtained from the FDA Orange Book.

Figure 2

Histological structure of mammalian skin. (a) Skin structure. The skin’s outermost layer is the stratum corneum, which is a nonviable tissue that provides most of skin’s barrier properties. The viable epidermis is an epithelial layer that serves to continuously renew the stratum corneum, among other functions. The dermis is a largely fibrous layer that provides skin’s mechanical support, as well as the skin’s vasculature and anchoring of sweat gland and hair follicle appendages. (Image of H&E stained porcine skin provided courtesy of Samantha Andrews, Georgia Institute of Technology). (b) Stratum corneum structure. Drug penetration across the stratum corneum is limited primarily by the lipids organized in bilayer structures (L) that fill the intercellular spaces between corneocytes (C). (Cryo-scanning electron micrograph provided courtesy of Joke Bouwstra, Leiden University and reproduced with permission from ref. 64).