**7.4. Acidifying effect of plasma on skin**

Acidifying effect was observed after applying plasma to stripped lipids from stratum corneum. A higher decrease of pH was observed in discharges, which produced a higher amount of NOx species. The same effect was observed on human skin, but after 30 min after plasma treatment, the pH of skin return to initial value [90]. The decrease of pH depends on parameters of the plasma discharge and the treatment time. Previous work has attributed the pH shift of water on plasma-treated lipids to the interaction of reactive species with the surface. Nitrates formed in water droplets could form nitric acid. NOx species could adhere on lipid surface or deposited nitric acid on the film surfaces by gaseous HNO3 [91]. The recovery of pH in the post-plasma phase was attributed to the decrease of acidifying agents on the substrate surfaces by both diffusion and desorption processes.

## **7.5. Skin etching and skin damage by plasma**

The etching effect of plasma is demonstrated in **Figure 11** by a cross section of the skin. The stratum corneum layer (the white part in (a) control sample) was removed after 20 tape stripping cycles, as shown in (b). After 30 s of atmospheric plasma jet irradiation, most of the stratum corneum layer was removed, as shown in (c). In the microplasma case, even after 5 min irradiation (d), the stratum corneum layer remained similar to the control sample, as shown in (a) [23]. Little difference in physical appearance was observed between the control pig skin sample and after microplasma irradiation. For the tape stripping test, surface asperity was decreased and after 10 s of atmospheric plasma jet irradiation, small pores (ranging from 40 to 100 μm) were observed. Physical damages on skin could be considered to arise from the electric field or an etching effect from bombardment with charged particles [92].

Surface potential can lead to a strong electric field across the skin and finally penetrate the skin to form holes. Holes were confirmed after longer operation (3–5 min) of atmospheric plasma irradiation. Pores and holes are shown in **Figure 12** after 10 and 30 s of operation of the plasma jet.

This physical damage could affect the barrier function of skin samples. When the effect of plasma jet was tested on PEN film, after 10 s of plasma jet irradiation, the surface potential increased to about 10% of the driven voltage. After long-term operation, it reached almost the same value as the driven voltage [23]. A similar problem could happen in electroporation but it uses very short operation times in the range of microseconds or milliseconds. High surface potential can induce current flow through the skin and it will increase the skin temperature and might affect cells of skin and cause thermal damage of skin [93]. On the contrary, the surface potential remained low in the microplasma case. The thickness of stratum corneum after 30 s of treatment of plasma jet is equivalent to 20 times of striping by tape. This is also confirmed by TEWL (**Figure 13**), which also shows the same values. On the other hand, TEWL after 5 min of microplasma irradiation of the pig skin sample, TEWL increased to almost double its original value, suggesting that the barrier properties were decreased through atmospheric microplasma irradiation but it is less effective than plasma jet [23].

Enhancement of Percutaneous Absorption on Skin by Plasma Drug Delivery Method http://dx.doi.org/10.5772/65116 125

**7.4. Acidifying effect of plasma on skin**

124 Advanced Technology for Delivering Therapeutics

by both diffusion and desorption processes.

jet.

**7.5. Skin etching and skin damage by plasma**

ma irradiation but it is less effective than plasma jet [23].

Acidifying effect was observed after applying plasma to stripped lipids from stratum corneum. A higher decrease of pH was observed in discharges, which produced a higher amount of NOx species. The same effect was observed on human skin, but after 30 min after plasma treatment, the pH of skin return to initial value [90]. The decrease of pH depends on parameters of the plasma discharge and the treatment time. Previous work has attributed the pH shift of water on plasma-treated lipids to the interaction of reactive species with the surface. Nitrates formed in water droplets could form nitric acid. NOx species could adhere on lipid surface or deposited nitric acid on the film surfaces by gaseous HNO3 [91]. The recovery of pH in the post-plasma phase was attributed to the decrease of acidifying agents on the substrate surfaces

The etching effect of plasma is demonstrated in **Figure 11** by a cross section of the skin. The stratum corneum layer (the white part in (a) control sample) was removed after 20 tape stripping cycles, as shown in (b). After 30 s of atmospheric plasma jet irradiation, most of the stratum corneum layer was removed, as shown in (c). In the microplasma case, even after 5 min irradiation (d), the stratum corneum layer remained similar to the control sample, as shown in (a) [23]. Little difference in physical appearance was observed between the control pig skin sample and after microplasma irradiation. For the tape stripping test, surface asperity was decreased and after 10 s of atmospheric plasma jet irradiation, small pores (ranging from 40 to 100 μm) were observed. Physical damages on skin could be considered to arise from the

Surface potential can lead to a strong electric field across the skin and finally penetrate the skin to form holes. Holes were confirmed after longer operation (3–5 min) of atmospheric plasma irradiation. Pores and holes are shown in **Figure 12** after 10 and 30 s of operation of the plasma

This physical damage could affect the barrier function of skin samples. When the effect of plasma jet was tested on PEN film, after 10 s of plasma jet irradiation, the surface potential increased to about 10% of the driven voltage. After long-term operation, it reached almost the same value as the driven voltage [23]. A similar problem could happen in electroporation but it uses very short operation times in the range of microseconds or milliseconds. High surface potential can induce current flow through the skin and it will increase the skin temperature and might affect cells of skin and cause thermal damage of skin [93]. On the contrary, the surface potential remained low in the microplasma case. The thickness of stratum corneum after 30 s of treatment of plasma jet is equivalent to 20 times of striping by tape. This is also confirmed by TEWL (**Figure 13**), which also shows the same values. On the other hand, TEWL after 5 min of microplasma irradiation of the pig skin sample, TEWL increased to almost double its original value, suggesting that the barrier properties were decreased through atmospheric microplas-

electric field or an etching effect from bombardment with charged particles [92].

**Figure 11.** Cross section of pig skin after atmospheric plasma irradiation, and tape stripping test. (a) Control sample, stratum corneum thickness: 18.09 ± 1.64 μm; (b) tape stripping test — 20 times, stratum corneum thickness: 5.99 ± 1.24; (c) plasma jet — 30 s, stratum corneum thickness: 3.49 ± 0.61; (d) microplasma — 5 min, stratum corneum thickness: 13.40 ± 1.46 [72].

**Figure 12.** Left: 10 s of treatment by plasma jet; Right: 30 s of treatment by plasma jet [72].

**Figure 13.** Variations of TEWL values before and after microplasma irradiation, tape striping test and plasma jet irradiation [72].
