Transdermal Drug Delivery Using Microplasma
J. Kristof , H. Miyamoto, M. G. Blajan and K. Shimizu
Shizuoka University, Nakaku, Johoku, Hamamatsu, 432-8561, Japane-mail: kristof.jaroslav.15@shizuoka.ac.jp, shimizu@cjr.shizuoka.ac.jp

temperature of skin during
treatment [°C]

Skin temperature is under 45°C –No temperature damage of the skin40

DBD microplasma

3940
3938

38

37

3736363535343433333232

31313030292903060

90

temperature of skin during
treatment [°C]Introduction. Stratum corneum is first barrier that protect
our body and does not allow penetration of amount ofobjects such as drugs. Intercellular route is very often used
for drug penetration when stratum corneum lipids are
extracted or their structure is changed. This study
investigate transdermal delivry of Cyclosporine A using
Micrplasma treatment.

Temperature safety

Ar microplasma discharge

120 150 180 210 240 270 300
time [s]Pharmacokinetics

Influence on penetration of drug
Intercellular space- Structure- Composition

Stratum corneum- Thickness

Etching effect of microplasma
Stratum corneum
Thickness = 20 μm

Stratum corneum
Thickness= 14 μm
AsymmetricCH3central compartment X1 represents blood. Cyclosporine A isdelivered to blood with flux k0i (in μg/hr) and it is eliminated fromthe body at rate constant ke. The second, peripheral compartment
X2 consists of tissues, bones, skin, etc. Drug exchange between thecentral and peripheral compartments is controlled by rate constants
k12 and k21.

Epidermal layer

200 μm200 μm

0.2
0.15
0.1
0.05
02700

2800

2900

3000

Shift to higher
wavenumbers

0.5
1.0
1.503100

wavenumber [cm-1]

Higher permeability

12shift of asymmetric-1
CH2 band [cm ]accumulative amount [g]Cyclosporine A penetration
Ar microplasma treatment
increased skin permeability toallow Cyclosporine A penetration

18Ar microplasma
DBD microplasma
no treatment

1614

No penetration
was observed in the case of12108“no microplasma treatment”

64

air microplasma treatment

200

24

6

8

Ar+H2O2 plasma treatment(or low amount of drug)

10 12 14 16 18 20 22 24

time [hr]1.4

Maximum penetration rate ofdrug is reached after 3 hoursRepeated microplasma treatment
A) Every 24 hours
B) Every 12 hours
3.5 mg/kg + TDD

80070020600

600500400
300
200
10000102030405060708090

100time (hr)DBD microplasma

1.2Cyclosporine A2flux [g/hr/cm ]After 24 hours,
14 μg of Cyclosporine A
was penetrated trough the skin

400 mg/ml of Cyclosporine A wasapplied to 225 cm2 (15x15 cm)(model)Combination of oral delivery withtransdermal delivery

1.0
0.8
0.6
0.4
0.2
0.002468

10 12 14 16 18 20 22 24time [hr]Repeated oral deliveryA) Every 24 hours (3.5 mg/kg)
B) Every 12 hours (3.5 mg/kg)
C) Every 24 hours (9 mg/kg)

concentration of Cyclosporine A in bloodstream (g/l)

CH2 asymmetric streching of lipids

concentration of Cyclosporine A in bloodstream ( g/l)

0.25

distance fromelectrode [mm]absorbance [a.u.]

Structure change of lipids of the stratum corneum

4060

80

100

60

80

100

3.5 mg/kg
A

400
200

0600

3.5 mg/kg
B

400
200

0
2000
1500

9 mg/kgC

1000
500
02040time (hr)Conclusions■ Applying of Ar microplasma increases permeability of the skin
■ Air microplasma does not increase skin permeability and gaseous H2O2 in mixture with Ar decrease (no penetration)■ Skin treatment is safe and no heat or electrical damege can happen■ It is possible to achieve therapeutic concentration of Cyclosporine A in the blood if 400 mg/ml of Cyclosporine A in propylene glycol is applied■ Microplasma drug delivery can decrease amount of the drug administered orally and to decrease interactions in gastrointestinal tract