Breaching the skin barrier through temperature modulations.

The impermeability of the stratum corneum often hinders the transport of molecules across the skin. Temperature modulations in the skin and the application of local heat both have the potential of circumventing this problem temporarily and reversibly and when applied, may aid in enhancing drug diffusion through the skin. A controlled and precise application of heat has the ability to create a cascade of events in the skin and thus aids in facilitating a faster movement of molecules into and across the skin. Possible mechanisms of enhancing drug permeation include: a) increase in drug diffusivity in the vehicle and/or in the skin, b) increase in partitioning and diffusion, c) disturbance in the lipid structure of the stratum corneum, and d) increased local blood flow. These mechanisms may operate individually or concurrently. The creation of micropores or channels in response to exposure to very high heat energy for a fraction of time is another technique that can facilitate the transport, known as thermal ablation. These micropores then serve as channels from where drug molecules can escape from formulations into the skin at a much faster rate than through passive diffusion. This review, therefore, summarises the effects that temperature modulations may have on the permeability of the skin. Physical techniques of heat induced skin ablation, such as chemical heating, thermoporation, radiofrequency induced thermal ablation, and laser induced thermal ablation are also presented in this review.