الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
Natural biopolymers have received great attention due to their safety, biocompatibility, biodegradation and their various applications in drug delivery systems and medical applications. Chitosan is one of the most important types of biopolymers that have achieved great success as antimicrobial and carrier for cancer drugs especially in the nano scale. This thesis aims to present a solution for chemotherapies’ drawbacks. The presented solution depends on designing two different types of smart drug delivery systems. This thesis is composed of 5 chapters. The first and second chapters presents a brief introduction and literature survey about the new advances and developments in the synthesis, characterization and applications of natural biopolymers and other synthetic polymers in cancer treatment via drug delivery systems using nano-carriers based on natural biopolymers and magnetic nanoparticles. Moreover, types of controlled release drug delivery systems and intelligent drug delivery systems that depend on using smart materials as natural or synthetic polymers are susceptible to various chemical, physical and biological influences. In this study we are focusing on two types of smart drug delivery systems: 1) Magnetic drug targeting system (MDT). 2) Smart polymeric therapy. In chapter 2, a general view about both chitosan & magnetic nanoparticles and their preparation methods, physical & chemical properties. In addition, using both nanoparticles in different biomedical applications highlighting using in drug delivery systems with focusing on some previous studies. Chapter 3 presents all used chemicals, analysis and characterizations that have done and preparation methods for Magnetic nanoparticles, magnetic nanoparticles modified with tri-sodium citrate, magnetic nanoparticles modified with l-lysine acid, both modified nanoparticles loaded with DOX & 5-Fu, chitosan modified nanoparticles with both glutamic & lysine acid and their drug loaded forms illustrated in chapter three. At the end, all obtained results are illustrated and discussed in chapter four. Chapter four is divided into two parts: First part titled “Biodegradable Functionalized Magnetite Nanoparticles as Binary Targeting Carrier for Breast Carcinoma” This part presents a different and effective therapeutic way for cancer disease specially breast cancer through targeting different types from chemotherapies (DOX & 5-Fu) depending on functionalization the surface of magnetite nanoparticles with two different function groups, one is carboxylic groups (COOH) from tri-sodium citrate by co-precipitation method via ligand exchange mechanism and using these carboxylic groups as a direct linker between magnetite and DOX via imine bond with conjugation efficiency 99.6%.The other function group is done through functionalization with lysine amino acid in new manner as a source for amino groups (NH2) via two-step transformation (TST) process. The NH2 groups on the surface of magnetite nanoparticles reacted with 5-Fu through electrostatic interaction force with conjugation efficiency 99%.To improve the bioactivity and biodegradability of conjugated DOX-Cit-MNPs & Fu-Ly-MNPs, they were coated with a thin layer from chitosan by encapsulation technique. The synthesized Cit-MNPs, Ly-MNPs and coated forms were investigated and their structures were confirmed via TEM & SEM to be spherical particles with diameter 7, 9 nm respectively and 45, 40 nm for chitosan coated forms respectively. crystalline structure for both carriers was confirmed by XRD to be pure magnetite (Fe3O4). The effect of pH on surface charge was studied and confirmed the positively charge of coated chitosan nanoparticles. Magnetic properties of MNPs which is a characteristic feature of MNPs in biomedical applications were investigated by (VSM). The small difference in magnetic susceptibility (MS) of 3 magnetite forms is may be due to the thin coated chitosan layer which, did not much affect the magnetic properties. These results and our interpretation were confirmed by TGA data. In-vitro release of DOX and 5-Fu was studied in acidic media reach 75% and 82.4% respectively but at physiological pHs was 28.6% and 36.5% after 168hr respectively. Cellular internalization mechanism was studied by florescence microscope and DAPI stain and we found that the internalization mechanisms of free drug models and CS / drug- functionalized MNPs are different. As free drug diffuses through the cell membrane but CS / drug- functionalized -MNPs are internalized the cells by endocytosis. The cytotoxicity of free drug and CS / drug- functionalized -MNPs was determined by IR% toward MCF-7 and normal cell line (WiSH). It was found that the CS / drug-functionalized-MNPs offered a sustained release for drug from the MNPs through the chitosan shell with low IR% in the first 24 hr, then increased after 72 hr without magnetic directing. By using an external magnetic field for free drug and CS / drug- functionalized -MNPs toward MCF-7 cell line, it was illustrated that the IR% highly increased to reach 71± 0.07 % in the first 24 hour and 98± 0.04% after 72 hour. The other important feature gained from CS / drug- functionalized -MNPs is its non-toxicity toward normal cells (WiSH) as free drug has high IR% toward normal cell to reach 76 ±0.04 % after 72 hr compared with CS / drug- functionalized -MNPs, which offered a protective mode for normal cells compared with free drug with IR% 22 ± 0.07 after 72 hour. Finally, we successfully synthesized biodegradable magnetic nano carriers for DOX and 5-Fu coated with chitosan which offer sustained release inside tumor cell, offer better cellular uptake with low cytotoxicity toward normal cells as a MDT therapy.