Microstructured transdermal systems for intradermal vaccine and drug delivery - PART I

Microstructured transdermal systems (MTS) have been attracting increased interest in recent years. The idea of using microstructures to pierce the stratum corneum to enhance drug delivery has been around for many decades in the form of multiple-tine devices for tuberculin testing and vaccine delivery, and in the form of larger numbers of even smaller structures at least since Ganderton was issued a patent on such devices in 1974.

However, for many years, this idea failed to meet its full potential because the technology to cheaply, accurately and reproducibly manufacture the microstructures was not available. In 1998, Henry disclosed methods of making the microstructures out of silicon, based on processes utilized in the semiconductor industry.

This disclosure, along with the growth of the biopharmaceuticals market and the difficulty in delivering macromolecules by routes other than injection, has sparked renewed interest in MTS technology. The intact skin, particularly the outermost layer called the stratum corneum, provides an incredibly robust barrier to delivery of all but a small fraction of relatively low molecular weight and lipophilic drugs. It is extremely difficult to achieve delivery of larger molecules through the skin in therapeutically relevant quantities, particularly macromolecules such as proteins, without perturbing the barrier function in some way.

An assortment of alternative active delivery technologies has been proposed based on the use of electric current, ultrasound, thermal ablation, pressure waves and lasers to disrupt the barrier function of the stratum corneum. MTS offer a comparatively straightforward alternative, which involves a simple mechanical disruption of the barrier.

MTS is particularly well suited to vaccine delivery because it provides a pain-free alternative to injection and unlike subcutaneous (SC) injections, the vaccine can be delivered in close proximity to the Langerhans cells in the epidermis. These two distinctions are responsible for a number of associated advantages.