الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Cancer treatment is one of the main challenges that face the scientific centers all over the world. The most used treatment for cancer is chemotherapy which is an application of systemic cytotoxic drug inside the patient. There are two main problems in chemotherapy that the cytotoxic (anti-cancer) drug is given systematically and cannot be localized in the tumor region (non-specificity) in most cases that lead to destroy the cancer cells as well as normal cells; and that cause the chemotherapy side effects like anemia, decrease in all blood cells count and platelets, nausea, vomiting, diarrhea, hair and nails loss and may cause a kind of blood toxicity.
The adverse side effects from conventional therapies and the resulting patient discomfort have encouraged researchers to explore site-specific therapies with the aid of drug loaded liposomes. Since the idea of site-specific therapy is to restrict treatment to the cancer site, thereby minimizing side effects and patient discomfort, drug loaded liposomes are attractive options because they based on releasing drugs in the tumor cells only without affecting the healthy tissue.
In our study two types of liposomes (USLs and TSLs) were prepared and were loaded with DOX to be used as ultrasound sensitive liposomes and thermosensitive liposomes for in vitro treatment of tumor in combination with ultrasound. USLs loaded with DOX were used in combination with pulsed ultrasound at frequency of 0.8 MHz with power intensity of 1 W/cm2. Ultrasound-triggered release of DOX from TSLs was conducted using a 0.8 MHz ultrasound system at intensity of 3 W/cm2.
The two types of liposomes (TSLs & USLs) were prepared by thin film evaporation method then characterized and investigated in terms of morphology, size and charge by transmission electron microscope and Zetasizer.
The cytotoxic effect on cells studied by MTT test as viability percentage, inverted microscope as morphology changes, confocal microscope to study the uptake and caspase3, GSH and DNA degeneration to study the apoptosis.
For USLs; they are completely spherical particles in shape, as shown by TEM, with the mean size 200 nm for liposomes and 250 nm for the liposomes encapsulating doxorubicin with the drug encapsulation efficacy (%EE) of 85.30.5%. The zeta potential of empty USLs is 2.38 0.32 mV; they do not have significant surface charge. This is expected because all the lipids used in their preparation were neutral and DOX-loaded USL was -2.39 1.84 mV.
For TSLs; DOX-TSLs are mostly unilamellar as shown by TEM, with the mean size 150 nm for liposomes and 200 nm for the liposomes encapsulating doxorubicin. The zeta potential for liposomes was 2.14 0.22 mV and -2.19 0.18 mV for DOX-loaded TSLs. The drug encapsulation efficiency (% EE) of DOX in loaded TSLs was evaluated as 89.7 0.8%.
Summary& Conclusion
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The experimental results showed that:
Hyperthermia and ultrasound waves generated by high and low intensity ultrasound respectively cause the release of DOX from DOX-loaded liposomes.
For US-sensitive liposomes through expansion of PFC that ruptures the Liposome and releases drug directly to the cell cytosol. For thermosensitive liposomes through hyperthermia that also rupture the liposome and release drug directly to cell cytosol.
Combination formula of DOX-USL and DOX-TSL cause significant increase in the cytotoxicity effect on HeLa cells compared to DOX alone; the viability decreased to 22.5 2.4% and 16.6 3.6%, increasing in caspase-3 concentration from 10.9 to 11.5ng/ml and decreasing GSH level from 26.1 to 24.5mU/ml and cause significant degradation in DNA.
II- Conclusion
Liposomes play an important role in the drug targeting for treatment of tumors.
DOX-USLs and DOX-TSLs enable a safe application to the tumor without affecting the healthy tissue which promises good therapeutic success.
The current use of US in clinical practice and the findings of our investigations make the combination of targeted therapy, nanotechnology, and focused ultrasound a promising platform for enhanced drug delivery and cancer treatment.