الفهرس 
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Abstract
The aim of the present study was to investigate the penetration efficiency of free
Methylene blue (MB),and Methylene blue (MB)–with insulin to the hairless diabetic mice
skin segment (in-vivo) using MN arrays iontophoresis (MN-IP) and, MN arrays
electroporation (MN-EP). Three different arrays of microneedle electrodes were used
(parallel, triangular, and circular). The in vivo permeability of MB and MB with insulin
were evaluated by measuring MB concentration in the skin, transported amount of MB,
cumulative amount of MB, mean flux rate, penetration depth of MB through excised mice
skin and blood glucose level before and after ionotophoresis.
The area enclosed by the MN array was equal to ~ 450 mm2 for the different shapes
of the electrodes array. Circular, triangular and parallel were the three different shapes of
the MN electrode array used
There were significant difference found in the permeation profiles between control
and experimental groups before and after putting the insulin on the mice skin, the diffusion
using circular, triangular and parallel MN-electrode array by applying (6, 9, 12V) were as
following:
• Experimental groups before putting the insulin : nine experimental groups will be
formed as follows,
GI: 6 volt IP + circular array MN electrodes.
GII: 6 volt IP + triangular array MN electrodes.
GIII: 6 volt IP + parallel array MN electrodes.
GIV: 9 volt IP + circular array MN electrodes.
GV: 9 volt IP + triangular array MN electrodes.
GVI: 9 volt IP + parallel array MN electrodes.
GVII: 12 volt IP + circular array MN electrodes.
GVIII: 12 volt IP + triangular array MN electrodes.
GIX: 12 volt IP + parallel array MN electrodes.
G x For each rat a paired control will be done, but without using the electric field.
• Experimental groups after putting the insulin : nine experimental groups will be
formed as follows,
G1: 6 volt IP + circular array MN electrodes.
G2: 6 volt IP + triangular array MN electrodes.
G3: 6 volt IP + parallel array MN electrodes.
G4: 9 volt IP + circular array MN electrodes.
G5: 9 volt IP + triangular array MN electrodes.
G6: 9 volt IP + parallel array MN electrodes.
G7: 12 volt IP + circular array MN electrodes.
G8: 12 volt IP + triangular array MN electrodes.
Summary & Conclusion
63
G9: 12 volt IP + parallel array MN electrodes.
G 10 For each rat a paired control will be done, but without using the electric field.
• Experimental groups using MB+gel : nine experimental groups will be formed as
follows,
GI: 6 volt IP + circular array MN electrodes.
GII: 6 volt IP + triangular array MN electrodes.
GIII: 6 volt IP + parallel array MN electrodes.
GIV: 9 volt IP + circular array MN electrodes.
GV: 9 volt IP + triangular array MN electrodes.
GVI: 9 volt IP + parallel array MN electrodes.
GVII: 12 volt IP + circular array MN electrodes.
GVIII: 12 volt IP + triangular array MN electrodes.
GIX: 12 volt IP + parallel array MN electrodes.
G x For each rat a paired control will be done, but without using the electric field.
• Experimental groups using MB+indulin+gel : nine experimental groups will be
formed as follows,
GI: 6 volt IP + circular array MN electrodes.
GII: 6 volt IP + triangular array MN electrodes.
GIII: 6 volt IP + parallel array MN electrodes.
GIV: 9 volt IP + circular array MN electrodes.
GV: 9 volt IP + triangular array MN electrodes.
GVI: 9 volt IP + parallel array MN electrodes.
GVII: 12 volt IP + circular array MN electrodes.
GVIII: 12 volt IP + triangular array MN electrodes.
GIX: 12 volt IP + parallel array MN electrodes.
G x For each rat a paired control will be done, but without using the electric field.
3- The following measurements were be done for each sample:
- The density and penetration depth of MB were determined throughout the skin
thickness using light microscope with digital camera.
- The concentration of absorbed MB, transported amount of MB, mean flux rate, and
cumulative amount of MB were be done at different voltages using different shapes
of MN arrays.
4- Data were fed to the computer and analyzed using IBM SPSS software package
version 22.0.Quantitative data were described using minimum and maximum, mean
and standard deviation and median. The correlations between values in groups were
done using Spearman Correlation. Correlation was significant at the 0.05 level,
sometimes was at 0.01 level.
Summary & Conclusion
64
Experimental groups to investigate the effect of electricity,
• group S(electric stress) consisted of 5 male rats expose to electric shock
• group N(non electric stress) consisted of 5 male rats without electric shock
(control)
5- Investigate the effect of electricity(as psychological stress) by measure the level of
blood glucose in group S after exposure to electric shock and in group N (without
electric shock) Measure the level of blood glucose of diabetic mice in group V and in
group D
Conclusions:
The following results are obtained:
• Increasing volt increasing the concentration of MB through the skin (μg MB) at 5 EP
followed by DC-IP (Square wave, 0.5A for 5 min) for studied groups using parallel
MN.
• Increasing volt decreasing the concentration of MB through the skin (μg MB) at 5 EP
followed by DC-IP (Square wave, 0.5A for 5min) for studied groups using circular
MN.
• Increasing volt increasing the average transported amount delivered (μg MB per cm2) at
5 EP followed by DC-IP (Square wave, 0.5A for 5min) for studied groups using
parallel MN.
• Increasing volt decreasing MB transported amount delivered (μg MB per cm2) at
5 EP followed by DC-IP (Square wave, 0.5A for 5min) for studied groups using
circular MN.
• Increasing volt increasing the mean flux rate of MB (μg / cm2/h) at 5 EP followed by
DC-IP (Square wave, 0.5A for 5min) for studied groups using parallel MN.
• Increasing volt decreasing the mean flux rate of MB (μg / cm2/h) at 5 EP followed
by DC-IP (Square wave, 0.5A for 5min) for studied groups using circular MN.
• Increasing volt increasing the penetration depth of MB at 5 EP followed by DC-IP
(Square wave, 0.5A for 5min) for studied groups using parallel MN.
• Increasing volt decreasing the penetration depth of MB at 5 EP followed by DC-IP
(Square wave, 0.5A for 5min) for studied groups using circular MN.
• Increasing volt decreasing the level of blood glucose in diabetic mice using three
different arrays of microneedle electrodes (parallel, triangular, and circular) by
insulin.
• The decrease ratio in blood glucose is the highest possible when using parallel
MN while using triangular MN the decrease ratio be lowest by insulin.
• The circular MN in between parallel and triangular MN.
• All results recommend applying a high voltage (12 V) with triangular MN or low
voltage (6 volts) with parallel MN to achieve a very high permeability of the drug.
Summary & Conclusion
65
• Increasing at the level of blood glucose in mice with a high fat diet which
exposure to electric shock (as psychological stress) than the high fat diet mice
wasnot expsed to electric shock.
Finally, the most important point in this work is to emphasize the role and
effectiveness of insulin in transdermal drug delivery to the skin layers MN arrays
regardless of the shape of the electrode and the applied voltage. All groups with insulin
recorded high permeability for the drug. To obtain a higher permeability of insulin,we
recommend using the parallel MN with the low voltage or a triangular MN with a hight
voltage. The development of diabetes increases with the presence of such factors as
obesity, pregnancy, infection, psychological stress, pancreatic or other endocrine disorders
and so on. So we should avoid exposure to psychological stress, follow a healthy diet and
reduce fat in our food.
5-a new device desiened by the student till under studing to treated the diabetic
through decrease the cell voltage to make the nervous system in parasymapthatic state (-
80mv), The idea of the device is based on the rule of all biological process is electrical
process, And that all hormones and glands of the body are subject to the work of the
pituitary gland and pituitary itself located under the nerve extension and subject to the
nervous system so, the nervous system is the control of all the processes of the body and
we can say that any damage or disorder in the body is a disorder in nervous system
interaction or in the electrical of the body ,the device based on change the depolarized
state (+50mv) to polarized state(-80mv)or close to it this device is close to voltage divider
with some editing and use aprogram langauge, we using the cell voltage to be the input
voltage.