الفهرس 
Title pageOnly 14 pages are availabe for public view
 |  | from | 112 |  |  |
| | | from | 112 | | |
Abstract
Breast cancer is a widespread, intricate, and diverse disease.The incidence of
cancer is rising in both industrialized and developing nations, making rendering it a leading
global source of death. Due to the intimate relationship between lifestyle variables and
cancer, cancer prevention may be both more effective and less expensive. In addition
finding novel and effective cancer therapies is a significant issue on a global scale. Natural
remedies have been utilized to cure a variety of illnesses, and they are now a significant
focus of drug development research. Numerous cascades, as cellular proliferation,
differentiation, apoptosis, angiogenesis, and metastasis, are modulated by these products,
notably phytochemicals, which have received significant research and have proven to have
anti-carcinogenic properties. The majority of effective anti-cancer medications already on
the market are phytochemicals or their equivalents, and some are even being tested on
humans. Sono-photodynamic therapy (SPDT) is a breakthrough and a modern technology
to eliminate tumor and affected tissues without affecting the healthy tissue adjacent to and
away from the tumor. This requires the use of a so-called sonophotosenstiser, which is
highly concentrated in the tumor area, which responds ideally to photonic energy and
ultrasonic waves, which works to stop tumor growth and elimination, which is a promising
technique to eliminate superficial and deep cancer tumors.
Transdermal drug delivery (TDD) is considered as a perfect alternative to
conventional drug administration. The drug or macromolecules can be delivered through
the skin into the bloodstream at a set rate using this delivery technique without causing any
discomfort.Hydrophilic, heavy-weight, charged substances cannot easily pass through the
stratum corneum into the systemic circulation due to the skin’s high lipophilicity. However,
many therapeutically effective pharmacological compounds have high molecular weights
and are hydrophilic, such as peptides.Many diverse strategies have been employed to get
over this barrier, including chemical and physical permeation enhancers including
iontophoresis, electroporation, and microneedles to encourage the skin absorption of
medications.
The present work aimed to study of microneedle-iontophoresis transdermal delivery
of Goniothalamus macrophyllus for activated cancer therapy using light and ultrasound.
An IR laser and US (in both puls.and cont. modes) were used as energy sources. The
underlying work was conducted with the goal of obtaining favourable results on applying
the SPDT in combination with transdermaly delivered SPDT sensitizer G. macrophyllus as
an advanced cancer treatment modality for the aiming of treatment EAC bearing mice. We
employed EP (5sec) with three different arrays of microneedle MN electrodes (parallel,
triangular, and circular) followed by Ip (5min) with different (6, 9, 12) volts, and infrared
laser with an ultrasound were used as our two energy sources (pulsed and continuous
wave).
In the current study, 120 male Swiss albino mice, 60–65 days aged and 205 gm
weighing were obtained. Only after EAC cancer was implanted upon subcutaneous
injection of Ehrlich ascites carcinoma cells the treatment trial launched. The Medical
Research Institute at Alexandria University’s ethical criteria was followed when using
experimental animals in the study methodology.
In vivo study groups were as follow; group 1: (50 mice); group 1a: 10 mice received
only saline and were kept without any treatment. group 1b: 10 EAC bearing mice received
only saline and were kept without any treatment. group 1c: 40 EAC bearing mice were
subjected to 6:12 volt EP (5 sec) + array MN electrodes IP (5 min) with (G. macrophyllus)
only. group 2: (laser irradiated group) 10 EAC bearing mice of this group were exposed
to Laser, for 3 min. group 3: (G. macrophyllus, laser group): 10 EAC bearing mice of this
group were subjected to 6 volt EP (5 sec) + array MN electrodes IP (5 min) with
(G. macrophyllus), then the tumor site was irradiated to laser light at same conditions of
group 2. group 4: (ultrasound group): 10 EAC bearing mice of this group were exposed
to continuous/pulsed ultrasound for 3 min. group 5: (G. macrophyllus, ultrasound group):
10 EAC bearing mice of this group were subjected to 6 volt EP (5 sec) + array MN
electrodes IP (5 min) with (G. macrophyllus), then the tumor site was irradiated to ultrasound
at same conditions of group 4. group 6: (combined group): 10 EAC bearing mice of this
group were exposed to laser light for 3 min, followed by ultrasound for 3 min. group 7:
(G. macrophyllus, combined group): 10 EAC bearing mice of this group were subjected to
6volt EP (5 sec) + array MN electrodes IP (5 min) with (G. macrophyllus), then the tumor
site was irradiated to laser light followed by ultrasound at same conditions of group 5.
The TDD and SPDT treatment evaluation:
Estimation mean of G. macrophyllus pore diameter penetrated through (µm),
transported (µg/cm2
), absorbed (µg/mg tissue), flux rate (µg/cm2
/5min) and
penetration depth (µm) at 5 sec electroporation microneedle (parallel, circular and
triangular) assisted TDD followed by DC-Iontophoresis (Square wave, 0.5 mA for
5min) at different volts (6, 9 and 12 volt) to Evaluate the effective TDD system.
Biochemical examinations were applied to detect serum ALT, AST, urea and
creatinine levels to detect effect of G. macrophyllus in combination with laser and
/ or ultrasound on liver and kidney functions.
Activities of some antioxidants were measured, namely; (GST, SOD, GR, Cat,
TAC) and (MDA) to detect the effect of G. macrophyllus in combination with
laser and / or ultrasound on antioxidant system and oxidative stress.
Molecular detection of P53, Caspase 3,9, Bax, Bcl2, TNFα and VEGF gene
expression using qRt-PCR to detect the effect of G. macrophyllus to detect the
effect of G. macrophyllus in combination with laser and / or ultrasound on pro and
anti-apoptotic as well as necrosis and angiogensis.
Evaluating the histological modifications in the tumour tissues after various
therapies using Hematoxylin and Eosin (H&E) stain using light microscope to
detect the effect of G. macrophyllus in combination with laser and / or ultrasound
on EAC tissue.