Feasibility of Atmospheric Argon Plasma for Improving Transdermal Drug Absorption
123
1,2,3
Nhat An Tran , Jaroslav Kristof , Marius Gabriel Blajan and Kazuo Shimizu
1Graduate School ofEngineering Shizuoka University

2 Graduate School of Science and Technology, Shizuoka University

3Organization for Innovation and Social Collaboration, Shizuoka University

1. Introduction
Drug delivery through the skin has been recognized as an important route. However, the transdermal route is still limited to delivery of small, lipophilic and low-dosedrugs. We investigated the effect of atmospheric pressure argon nonthermal plasma irradiation on reducing skin barrier function as a promising solution.
Atmospheric pressure nonthermal plasmas has been demonstrated to be appropriate for skin treatment such as wound healing, tissue regeneration or wrinkle treatment. In
this study, a promotion of transdermal drug absorption by the atmospheric argon plasma irradiation was investigated. The results were analyzed by using an infrared totalreflection absorption measurement (ATR) method and transepidermal water loss (TEWL) measurement.

2. Experiment Setup and Method
Microplasma

Tape Stripping• Target: Yucatan micropig skin

• Target: Yucatan micropig skin

• Power Source: 27.1 kHz AC• Tape: Scotch Tape

• Applied Voltage: 700 V (0-P)• Number of tape stripping: 10, 20 cycles• Process Gas: Argon• Pressure on the skin: 165 g/cm2• Exposure time: 1 min, 5 min• Exposure distance: 7 mm

Advantages of Microplasma

Voltage

500 V/div

1 cm

10 µs/div

Stratum corneum (SC) layers
were physically removed

Barrier function of the SC wascertainly reduced

ATR Method

TEWL Measurement

 No need of costly vacuum enclosures

GND Including highly reactive species,
charged species

GND
500 mA/div

Pressure clamp Current• Prism: Diamond Simple equipment structure

10 µs/div• Resolution: 4.0 cm-1

Increased TEWL

• Cumulated number: 64 times

Reduced barrier function

3. Results
ATR-FTIR Analysis

TEWL Measurement
60

AAMI = Atmospheric Argon Microplasma Irradiation

50

TST = Tape Stripping Test

① Increase in plasma
exposure time

Keratinamide IKeratin
amide IICH2
symmetricstretch

TEWL [g/m2h]

FTIR = Fourier Transform Infrared Spectrometer

Increase in plasma
exposure time4030

Increase in TEWL value
2010CH2symmetricstretch0

Reduction in the CH2C=Ostretching

Control

stretching modes absorbance② Increase in the number oftape strips

AAMI
5 min

TST
10 times

TST
20 times

Microscopic observation

1.2

Decrease in asperity of stratum corneum layer

1Absorbance [a.u.]

AAMI
1 min

Barrier properties of theskin were decreased

CH2 symmetric①

CH2 asymmetric

0.8

②0.6

Reduction in the CH2 stretchingmodes absorbanceMicroplasma
irradiation

0.4
0.2

Damage on the skin

Disturbance in the SC lipids0Control

AAMI

AAMITSTTST

1 min

5 min

10 times

20 times(a) Control(b) AAMI 5 min(c) TST 20 times

4. Conclusions
 The reduction in the CH2 stretching peaks reflects the disturbance in the SC lipids after AAMI.
 TEWL value was decrease for both of AAMI and TST, which suggests that the barrier function of the SC was decreased.
 The microscopic observation indicated that AAMI does not lead to physical damages on a skin.

Alternative technology
for normal injection needles