Microsecond thermal ablation of skin for transdermal drug delivery

Abstract

Thermal ablation is a promising mechanism to increase permeability of the skin's outer barrier layer of stratum corneum while sparing deeper living tissues. In this study, finite element modeling predicted that the skin surface should only be heated on the microsecond timescale in order to avoid significant temperature rises in living cells and nerve endings in deeper tissue. To achieve such short thermal pulses, we developed a microdevice that rapidly heats a few microliters of water by an electrical discharge and ejects the resulting superheated steam at the skin surface on a timescale on the order of 100 μs. According to its design, we showed that this microdevice selectively removed stratum corneum of cadaver skin without significantly removing deeper tissue. This one-dimensional depth control was supplemented through the use of a masking film containing 100 μm-diameter holes placed on the skin surface during ablation to define the ablated skin area and thereby provide three-dimensional control over tissue removal. Using this approach, thermal ablation increased skin permeability to sulforhodamine B and bovine serum albumin by at least 1000-fold in vitro. We conclude that microsecond thermal ablation of skin can selectively remove stratum corneum and thereby dramatically increase skin permeability for transdermal drug delivery.