School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
J Control Release. 2011 Aug 25;154(1):58-68. doi: 10.1016/j.jconrel.2011.05.003. Epub 2011 May 17.
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.
热消融是一种很有前途的机制，可以增加皮肤外层角质层的通透性，同时保护深层的活组织。在这项研究中，有限元模型预测，为了避免深层组织中的活细胞和神经末梢的温度显著升高，皮肤表面只需在微秒时间尺度上加热。为了实现如此短的热脉冲，我们开发了一种微器件，通过电放电迅速加热几微升的水，并在 100 μs 的时间尺度上将产生的过热蒸汽喷射到皮肤表面。根据其设计，我们表明这种微器件可以选择性地去除尸体皮肤的角质层，而不会显著去除深层组织。通过使用含有 100μm 直径孔的掩蔽膜来补充这种一维深度控制，该掩蔽膜在消融过程中放置在皮肤表面上以定义消融的皮肤区域，从而对组织去除提供三维控制。通过这种方法，热消融使体外磺基罗丹明 B 和牛血清白蛋白的皮肤通透性至少增加了 1000 倍。我们得出结论，皮肤的微秒热消融可以选择性地去除角质层，从而极大地增加皮肤的通透性，以实现经皮药物输送。
