The effect of heat on skin permeability

Abstract

a b s t r a c tAlthough the effects of long exposure ( 1 s) to moderate temperatures (≤100 • C) have been well characterized, recent studies suggest that shorter exposure (<1 s) to higher temperatures (>100 • C) can dramatically increase skin permeability. Previous studies suggest that by keeping exposures short, thermal damage can be localized to the stratum corneum without damaging deeper tissue. Initial clinical trials have progressed to Phase II (see http://clinicaltrials.gov), which indicates the procedure can be safe. Because the effect of heating under these conditions has received little systematic or mechanistic study, we heated full-thickness skin, epidermis and stratum corneum samples from human and porcine cadavers to temperatures ranging from 100 to 315 • C for times ranging from 100 ms to 5 s. Tissue samples were analyzed using skin permeability measurements, differential scanning calorimetry, thermomechanical analysis, thermal gravimetric analysis, brightfield and confocal microscopy, and histology. Skin permeability was shown to be a very strong function of temperature and a less strong function of the duration of heating. At optimal conditions used in this study, transdermal delivery of calcein was increased up to 760-fold by rapidly heating the skin at high temperature. More specifically, skin permeability was increased (I) by a few fold after heating to approximately 100-150 • C, (II) by one to two orders of magnitude after heating to approximately 150-250 • C and (III) by three orders of magnitude after heating above 300 • C. These permeability changes were attributed to (I) disordering of stratum corneum lipid structure, (II) disruption of stratum corneum keratin network structure and (III) decomposition and vaporization of keratin to create micron-scale holes in the stratum corneum, respectively. We conclude that heating the skin with short, high temperature pulses can increase skin permeability by orders of magnitude due to structural disruption and removal of stratum corneum.

Transdermal and Topical Delivery to the Skin

“…It is based upon transiently heating a selective portion of the skin to 100° (for micro-to milliseconds) to make a perforation into the SC. In that time frame, the heat does not reach viable tissues, but the mobility across the skin is signifi cantly increased [ 32 ].…”

Enhancement of Percutaneous Absorption on Skin by Plasma Drug Delivery Method

“…In the range of 150-250°C, transdermal flux increased by two orders, attributable to disruption of stratum corneum keratin network structure. Above 300°C, transdermal flux increased by three orders, attributable to decomposition and vaporization of the stratum corneum [83].…”

Lidocaine permeation from a lidocaine NaCMC/gel microgel formulation in microneedle-pierced skin: vertical (depth averaged) and horizontal permeation profiles

“…Collagen based porcine skin has a denaturation temperature of 37˚C [35,36]. Also, dry heating (e.g., a thermal effect generated by passing hot air) at temperature ranging from 100˚C to 315˚C on skin surfaces result in the weakening of mechanical properties and disorder of keratin network of the skin [37]. Adaptation of dry heat ablation of skin at high temperatures occurred during micro second time frames as longer durations would have denatured more skin proteins below the upper layers [37].…”

“…Also, dry heating (e.g., a thermal effect generated by passing hot air) at temperature ranging from 100˚C to 315˚C on skin surfaces result in the weakening of mechanical properties and disorder of keratin network of the skin [37]. Adaptation of dry heat ablation of skin at high temperatures occurred during micro second time frames as longer durations would have denatured more skin proteins below the upper layers [37]. Also, prolonged dry heat ablation would burn skin into powdered carbon ash and lidocaine will be undetectable by LC-DA methods as the chemical structure would be changed completely.…”