الفهرس 
Title pageOnly 14 pages are availabe for public view
 |  | from | 128 |  |  |
| | | from | 128 | | |
Abstract
Iontophoresis is a method of transdermal drug delivery using electric current. Electrical energy assists the movements of ions across the SC according to the basic electrical principle that like charges repel each other and opposite charges attract each other. This method depends on applying low voltage to supply continuous DC of (0.5 mAmp/ cm² or less).
The aim of this work is to study the role of electric field parameters on the degree of transdermal delivery of MB (as a drug model) through pig skin with and without stimulation (electroporation).
In this work the following things were used:-
(a) Stimulating circuit: used for skin stimulation using pulsed sine shape electric field. This circuit composed of transformer, variac, and diode, such circuit capable to produce pulsing sine shape electric field has an electric potential upto 240 V. To stimulate skin, the electric potetial was changed to give (12.5v, 25v, 50v, 100v, and 200v) with exposure duration of 5 seconds just before iontophoresis application.
(b) Iontophoresis circuit: this circuit was constructed to produce DC current to enhance MB penetration through the skin. The DC currents taken from the circuit were 0.2 mAmp/cm² and 0.4 mAmp/cm², the iontophoresis duration was either 30 min or 60 min.
(c) Methylene blue: pure MB was used as a drug model because its cationic nature makes it a suitable model for a number of photosensitizer and chemicals with similar characters.
(d) Pig skin: was used because it has histological properties comparable to human skin with similarities in epidermal thickness and composition, dermal structure, lipid content, and general morphology.
(e) Electrode and rings: two Ag/AgCl electrodes and rings (0.9 cm in diameter) were used.
(f) The groups:
Seven main pig skin groups used in the work classified as follow:
a- G Ι: 40 samples were stimulated by pulsing sine shape electric field; the pulse height used in this group was 6.5 V, and its duration 5 seconds. The group was divided into four subgroups, each one contained 10 samples:
G Ιa: exposed to DC current of 0.2 mAmp/cm2 for 30 min.
G Ιb: exposed to DC current of 0.4 mAmp/cm2 for 30 min.
G Ιc: exposed to DC current of 0.2 mAmp/cm2 for 60 min.
G Ιd: exposed to DC current of 0.4 mAmp/cm2 for 60 min.
b- G ΙΙ: 40 samples were stimulated by pulsing sine shape electric field; the pulse height used in this group was 12.5 V, and its exposure duration 5 seconds. The group was divided into four subgroups; each one contained 10 samples treated exactly as the previous subgroups.
c- G ΙΙΙ: 40 samples were stimulated by pulsing sine shapes electric field; the pulse height used in this group was 25 V, and its exposure duration 5 s. The group was divided into four subgroups; each one contained 10 samples treated exactly as the previous subgroups.
d- G ΙV: 40 samples were stimulated by pulsing sine shape electric field; the pulse height used in this group was 50 V, and its exposure duration 5 s. The group was divided into four subgroups; each one contained 10 samples treated exactly as the previous subgroups.
e- GV: 40 samples were stimulated by pulsing sine shape waves; the pulse height used in this group was 100 V, and its exposure duration 5 s. The group was divided into four subgroups; each one contained 10 samples treated exactly as the previous subgroups.
f- GVІ: 40 samples were stimulated by pulsing sine shape electric field; the pulse height used in this group was 200 V, and its exposure duration 5 s. The group was divided into four subgroups; each one contained 10 samples treated exactly as the previous subgroups.
g- G◦: 40 samples weren’t stimulated by pulsing sine shape electric field, divided into four subgroups; each one contained 10 samples treated exactly as the previous subgroups.
After application of iontophoretic process with and without electroporation, the following parameters were measured:
A. The physical parameters
1. The concentration of absorbed MB (mg MB /g tissue).
2. Transport of MB across the skin surface (μg/cm²).
3. The average flux of MB (μg/cm²/min).
4. The ohmic resistance of the skin (kΩ/cm).
5. Dielectric properties of the skin.
B. histological parameters:
1. Penetration depth of MB across pig skin (μm).
2. Flux rate (μm/ min).
The obtained data were statistically analyzed using student t-test to determine the best and suitable stimulating and iontophoretic electric parameters.
B. Conclusion:
• The highest MB concentration in mg/g tissue (0.239± 0.011) and lowest ohmic resistance (kΩ/cm) (3.15±0.223) for skin were obtained after skin stimulation with 12.5 V (exposure dose 21.7 V.s).
• Dielectric properties of skin in the range of 10 Hz- 100 KHz revealed change in the dielectric dispersion curves immediately after skin stimulation.
• Conjunction of iontophoresis with electroporation was more effective for MB delivery through the skin, than iontophoresis alone, the conjunction between two methods give higher concentration of (1.168±0.013) for stimulation of 12.5 V and exposure of 17.28 joule while the value of exposure 17.28 joule alone without any stimulation was (0.3279±0.024).
• MB delivery depends on iontophoretic current density; i.e. MB concentration was higher when we used current density 0.4 mAmp/cm² (0.3279± 0.024) than that obtained when we used 0.2 mAmp/cm² (0.2316± 0.035) at the same exposure time (60 min)
• MB transport in (μg/cm²) gives its highest value after skin exposure to 12.5V (522.49± 62.37).
• The highest value of average flux (μg/cm²/min) was at exposure 12.5V and energy of 8.64 joule (0.4 mAmp/cm², 30 min) it was (14.69±0.9).
These data were confirmed using a histological quantification procedure, measured the penetration depth of MB.
• Histological data showed that MB delivery (μm) was much greater using iontophoresis after electroporation than that delivered by iontophoresis alone. the combination between two methods give higher penetration depth of (105.26±1.97) for stimulation of 12.5 V and exposure of 17.28 joule while the value of exposure 17.28 joule alone without any stimulation was (46.93±3.79).
• The flux rate of MB (μm/min) was affected by iontophoretic energy; the highest value was at 8.64 joule (0.4 mAmp/cm², 30 min) following electroporation at 12.5V (2.972± 62.37).
from the histological data we observed that, the most MB amount was transported through the skin at the beginning of the iontophoresis process (i.e. at the first 30 min) then reached to a steady state, at the second 30 min.
Finally the results presented in this work can be interpreted only if we considered that, the electroporation of the skin caused disorganization of SC lipid structure and enhanced drug or chemical delivery into the skin. Reduction in skin resistance, increased permeation of SC implying the creation and enlargement of opening through which electrolyte flow. The dielectric properties changes after electroporation confirmed this hypothesis. That is to say, electroporation followed by iontophoresis seemed to be more effective procedure for drug delivery through the skin.