الفهرس 
GENERAL INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Breast cancer remains an overwhelming health burden, as it is a leading cause of female death worldwide. It was found that, approximately one-third of human breast tumors are reported to be estrogen-dependent. Ever since, breast cancer was linked to estrogen level in the blood and various attempts have been made to antagonize estrogen’s biological effects as a therapeutic strategy.
On the other hand, nanotechnology has presented a promising approach to overcome the limitations of conventional anticancer therapy, as nanoparticles (NPs) exhibit interesting characteristics including small sizes, large surface-to-volume ratios, high drug loading and biocompatibility. Thus, NPs confer specific physical and chemical properties at the cellular and molecular levels not attainable with the drug moieties themselves.
Natural polymers, such as polysaccharides and proteins, are interesting alternative to synthetic polymers that are commonly used in the medical and pharmaceutical industries. Natural proteins are considered the ideal materials used as carrier polymers for medical applications, as they are digestible, metabolizable, biodegradable and biocompatible.
Zein is one of the best understood biomacromolecule abundantly available and utilized for various industrial and medical applications. The hydrophobic nature of zein can be exploited for sustained drug delivery applications. This may improve therapeutic efficacy and reduce the dosing frequency that lead to enhanced patient compliance and convenience, while reducing the severity and frequency of side effects.
This thesis is a focus highlighting on the usage of two novel drug-loaded zein NPs delivery systems for the treatment of breast cancer.
The current work is divided into three parts:
PART ONE: Novel Tumor-Targeted Zein Nanospheres for Parenteral Co-Delivery of the Poorly Soluble Anticancer Drugs, Exemestane and Luteolin in Breast Cancer Therapy
EXM is a potent third generation steroidal irreversible inhibitor of aromatase. EXM is indicated for the first line treatment of hormone-receptor-positive advanced breast cancer in women. Unfortunately, delivery of EXM via the oral route faces massive obstacles because of poor aqueous solubility, low membrane permeability and low bioavailability.
The resistance development to anticancer drugs is the major clinical concern during endocrine therapies. EXM resistance mechanism relies on the weak estrogenic properties of this aromatase inhibitor to activate EGFR signaling pathways.
The dietary flavone, LUT, was found to be a potent anticancer phytochemical through different mechanisms of action. Since LUT has an inhibitory effect on EGFR-mediated cell survival, it was logic that, it can overcome EXM resistance.