BRIEF COMMUNICATION Lack of Pain Associated with Microfabricated Microneedles

H ypodermic needles are effective at bolus delivery of drugs, but cause pain during insertion and are not ideally suited for delivery over extended periods. Transdermal patches address these shortcomings (1), but are extremely limited in application because most drugs are unable to cross skin at therapeutic rates (2,3). As a novel alternative, we have used microfabrication technology to make microneedles that pierce into the skin far enough to permit drug delivery, but are short and thin enough to avoid causing pain. The skin’s stratum corneum provides the greatest barrier to drug transport into the body (4). Because this layer contains no nerves, a microneedle that crosses stratum corneum without going much deeper should be capable of delivering drugs into the permeable regions of skin without stimulating nerves found deeper in the tissue. Previous work has demonstrated that microneedles of the same design used in this study are capable of piercing human skin and increasing skin permeability by orders of magnitude to small molecules and proteins for many hours in vitro (5,6). Our objective was to test the hypothesis that silicon microneedles are small enough to avoid causing pain by comparing sensation associated with microneedle application to the forearm of human subjects to that caused by a 26-gauge needle (positive control) and a smooth silicon surface (negative control). Methods