Permeability of thermally damaged skin V: Permeability over the course of maturation of a deep partial-thickness wound

Flynn, Gordon L.; Behl, Charanjit R.; Linn, Edwards E.; Higuchi, William I.; Ho, Norman F.H.; Pierson, Carl L.

doi:10.1016/0305-4179(82)90088-2

Cited by 8 publications

(2 citation statements)

References 7 publications

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“…As an example of extended heating at moderate temperature, exposure to 40 • C for 4 h has been shown to increase human skin permeability to a hydrophobic drug (fentanyl) by 4-fold via a mechanism believed to involve stratum corneum lipid fluidization (Shomaker et al, 2000). Exposure to 80 • C for 15 s showed a 12-fold increase in porcine skin permeability to another hydrophobic model drug, butanol (Flynn et al, 1982). Other studies have similarly measured increased skin permeability after heating (Jain and Panchagnula, 2003;Murthy et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

The effect of heat on skin permeability

Park¹,

Lee

Kim

et al. 2008

International Journal of Pharmaceutics

110

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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.

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Section: Introductionmentioning

confidence: 99%

The effect of heat on skin permeability

Park¹,

Lee

Kim

et al. 2008

International Journal of Pharmaceutics

110

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“…As an example of long heating at moderate temperature, exposure to 40 • C for 4 h has been reported to increase human skin permeability to a hydrophobic drug (fentanyl) by fourfold via a mechanism involving stratum corneum lipid fluidization [20]. Exposure to 80 • C for 15 s has been shown to increase porcine skin permeability to a hydrophobic compound, butanol [21].…”

Section: Introductionmentioning

confidence: 99%

A thermal microjet system with tapered micronozzles fabricated by inclined UV lithography for transdermal drug delivery

Yoon

Park²,

Lee

et al. 2011

J. Micromech. Microeng.

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Transdermal drug delivery can be enabled by various methods that increase the permeability of the skin's outer barrier of stratum corneum, including skin exposure to heat and chemical enhancers, such as ethanol. Combining these approaches for the first time, in this study we designed a microdevice consisting of an array of microchambers filled with ethanol that is vaporized using an integrated microheater and ejected through a micronozzle contacting the skin surface. In this way, we hypothesize that the hot ethanol vapor can increase skin permeability upon contacting the skin surface. The tapered micronozzle and the microchamber designed for this application were realized using proximity-mode inclined rotational ultraviolet lithography, which facilitates easy fabrication of complex three-dimensional structures, convenient integration with other functional layers, low fabrication cost, and mass production. The resulting device had a micronozzle with an orifice inner and outer diameter of 220 and 320 μm, respectively, and an extruded height of 250 μm. When the microchamber was filled with an ethanol gel and activated, the resulting ethanol vapor jet increased the permeability of human cadaver epidermis to a model compound, calcein, by approximately 17 times, which is attributed to thermal and chemical disruption of stratum corneum structure. This thermal microjet system can serve as a tool not only for transdermal drug delivery, but also for a variety of biomedical applications.

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