Dissolving microneedles: safety considerations and future perspectives.

Abstract

As the largest and most accessible organ in the body, with a surface area of 1.5–2 m 2 , the skin is an enticing target for drug delivery. Delivery of medication through the skin has expanded beyond the initial brief of topical delivery for local action to the transdermal application of drugs designed for systemic absorption and action. The principal obstacle to such transport is that of the stratum corneum, the outermost skin layer. To enable the delivery of a wider range of drug compounds and overcome the permeability barrier of the skin anatomy, microneedles (MNs) were born. MNs are a mechanical method of skin poration, first conceptualized in the 1970s [1]. Since manufacturing advances allowed the first practical realization in 1998 [2], MNs have demonstrated great promise as a novel drug delivery platform. MN arrays consist of a plurality of tiny projections on the micron scale arranged on a base plate. By bypassing the stratum corneum, its rate-controlling effect is nullified, allowing transdermal deliv ery of a much wider range of drug molecules than would be possible by passive diffusion, including macromolecules, such as biologics and vaccines. With a typical average length of 50–900 μm, MNs are long enough to penetrate to the dermis, but are short and narrow enough to avoid stimulation of dermal nerves or puncture of dermal blood vessels. Initially, MNs were typically prepared from silicon and metal. However, there is now great interest in the use of US FDA-approved polymeric materials for MN manufacture [3]. These materials are often inexpensive and widely available, amenable for MN manufacture without the use of harsh processing conditions, for example, elevated temperatures. Prepared from water-soluble polymers, dissolving MN arrays have the drug incorporated into the MN formulation and upon insertion, the MNs dissolve, releasing the drug in the viable skin layers. Such a strategy offers a number of advantages for the patient. As the MNs dissolve upon application, the dosage form is effectively self-disabling, meaning that not only is the reinsertion of the needles into another patient impossible, but there is also no risk of needle-stick injury to the healthcare professional, thereby reducing the overall risk of infection transmission. The question of disposal of MNs is also simplified, as with no sharp waste remaining, there is no need for safe disposal. Dissolving MN arrays have been used to deliver a range of compounds, from hydrophilic, low molecular weight drugs, to larger biopharmaceutical molecules, demonstrating the ability of such a platform to enhance transdermal delivery [4]. Indeed, the technology has progressed to human trials, with positive results recently published from a Phase 2a study for the delivery of human parathyroid hormone using a biodegradable MN technology called MicroCor ® , developed by Corium International, Inc. [5]. Another promising application for dissolving MNs is that of vaccination, capitalizing on the rich immune cell population in the skin,