الفهرس 
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Abstract
Chemotherapy remains an aggressive technique for the clinical treatment of cancer, but it poses a great risk to human health and life. Chemotherapy often presents with instability and poor biodistribution, resulting in impaired pharmacokinetics. The cellular targeting feature of the biocompatible drug delivery system can significantly improve the therapeutic effect against cancer. Drug delivery and nanotechnology together have recently received great attention, owing to their properties, including decreased drug resistance, increased drug stability, surface area, and dissolution rate. Nanotechnology was developed as an innovative bundling strategy by delivering several therapeutic agents in a single nanocarrier. The combination of two or more chemotherapies to enhance anticancer efficacy is a commonly used strategy in cancer treatment. Furthermore, to overcome the defect of minimizing the dosage of the drug, and the side effects of single drugs, two drug-loaded NPs has been generally accepted as a feasible technique. Magnetically controlled drug delivery is attracting more interest due to its ability to carry a large dose of the target drug, causing a high topical concentration, and thus high efficacy while avoiding toxicity. Superparamagnetic Fe3O4 NPs has received great interests in the biomedical field for drug and target gene delivery systems, due to their outstanding magnetism, biocompatibility, low toxicity, biodegradability, eco-friendliness, and low cytotoxicity in the iron-rich bloodstream. ZnO is considered a modern drug delivery system homeostasis due to its function in maintaining crucial cellular processes including DNA replication, oxidative stress, cell cycle progression DNA, repair, and apoptosis. To overcome the drawback of poor biodegradation of inorganic NPs, biopolymers are used as carrier due to their biocompatibility, biodegradability, and non-toxic nature. The PHB is a highly biocompatible, naturally biodegradable, and hydrophobic biopolymer. The PHB is used in biomedical purposes, owing to its crystallinity, a relatively high melting point and sufficient hydrolytic stability. It is physiologically present in the human blood; hence, its appropriate derivatives have no acute cytotoxicity. The main feature is that when PHB is used as an implant, the body does not produce any immune response and does not reject the implantation. The aim of this work was directed to: a- Synthesis of new biodegradable, non-toxic, and biocompatible nanomedicine with high efficacy for cancer treatment and magnetic properties that help us control it through the magnetic field to reach cancer cells without harming healthy cells. b- Synthesis of highly efficient and inexpensive electrochemical sensors, which could be used to monitor the drug release from drug carriers as well as for sensitive detection of co-mixed anticancer drugs in biological fluids without any interference from fluid excipients. In this context, the thesis is divided into 3 chapters as follows: Chapter 1: This chapter provides a general introduction about hyperthermia and their types, ART, DA, CUR, drug delivery, biopolymers, biodegradable polymer, Polyhydroxyalkanoates and their applications, poly (3- hydroxy butyrate), and their biosynthesis , cell and their synthesis, CS, conductive polymer and their properties and application, Ppy and their application, metal oxide NPs, semiconducting metal oxide, magnetic NPs, zinc oxide NPs, electroanalytical method, voltammetry and their types and working sensors. Then, this part ended with a literature survey on application of PHB and their composites as drug delivery system and literature survey on modified electrode for ART, and DA. Chapter 2: This chapter concerns the experimental part. The chemicals and their resources were mentioned. The steps includes synthesis of magnetite, ZnO NCs, ZnO/ magnetite NC, Ppy@ZnO/Fe3O4 NC, extraction of cellulose from Okra, synthesis of amine-functionalized cellulose nanocrystal, cell-g-PHB, cell-g-PHB-Fe3O4/ZnO NC, PHB-Co-CS copolymer, PHB-Co-CS-Fe3O4/ZnO NC, preparation of analytical liquors, unmodified and modified graphite past sensor, loading of DA into Fe3O4/ZnO NC, coating of Fe3O4/ZnO NC NPs loaded DA by cell-g-PHB, synthesis of ART loaded onto cell-g-@PHB-Fe3O4/ZnO, and cell-g-@PHB-DO@Fe3O4/ZnO nanocarriers, encapsulation of ART/CUR onto PHB-Co-CS copolymer, synthesis of ART loaded onto PHB-Co-CS- CUR@Fe3O4/ZnO nanocarriers. The techniques used for loading measurement. The techniques used for release measurement and kinetics mathematical equations were mentioned. The techniques and measurements for characterization of nanocomposites were mentioned. In this part, the techniques used to evaluate antibacterial, and anticancer activity were explained. Chapter 3: This chapter concerns the results that are summarized as follows: Part I: Herein, a voltammetric sensor has been successfully developed for ultrasensitive and reproducible detection of Artesunate (ART) and Dopamine HCl (DO) using Ppy@ZnO/Fe3O4 core-shell nanocomposite ([PZM] NS) modified graphite paste sensor (MGPS) via the differential pulse adsorptive stripping voltammetry (DP-AdCV). Physicochemical features of ZnO/Fe3O4, and Ppy@ZnO/Fe3O4 core-shell nanocomposites were characterized by using FTIR, XRD dynamic light scattering, transmission electron microscopy and scanning electron microscopy. The [PZM] emerges with good core-shell nanocomposite and a specific surface area of 28.5 m2/g (0.0247 cc/g) compared to ZnO/Fe3O4 [ZM] 5.43 m2/g (0.0111 cc/g). The morphological examination of [PZM] reveals a spherical core shell nanostructure with an increase in average diameter to be 40.5 nm compared with the average [ZM] diameter of 10 nm. Subsequently, the particle size distribution of [ZM], and [PZM] were measured to be 805, 3225.67 nm with polydispersity index of 1 and 0.605, respectively. The [PZM] modified graphite paste sensor MGPS provided the best electroactive surface area (0.078 cm2) with minimal electrocatalytic activity (Rst= 370 Ω) compared to other as-prepared sensors. Under standard optimum conditions, the MGPS possessed a low detection limit of 0.24 pM (1.27 μA/pM), and 0.03 pM (0.386 μA/pM) for Artesunate (ART) and Dopamine HCl (DO) respectively. As well, detection limits were found to be 0.75 and 0.09 pM for ART mixed with 0.7 pM of DO and DO in the presence of 2.0 pM of ART drug, respectively. Furthermore, the MGPS reveals proper repeatability, reproducibility, and storage stability. The modified voltammetric sensor was able to detect both co-mixed ART and DO concentrations, without interference during the routine analysis. Part II: In this part, the cells were extracted from okra bears, and treated with sulfuric or phosphoric acid to produce Scell, and Pcell nanocrystals, respectively. Amine functionalized carboxymethyl cellulose, Scell, and Pcell were prepared by reactions with 3- aminopropyl trimethoxy silane, methacrylate, and diamine. The Cell-g-PHB copolymers were synthesized by conjugation of the carboxyl group of PHB to the amino group of cell-NH2 with EDC as a condensing agent, mixed with Fe3O4/ZnO core/shell, and loaded with DA, and ART drugs. The effect of adding different contents of Fe3O4/ZnO NCs on the loading, and release of drugs was evaluated. Energy dispersive X-ray measurements indicate that the presence of Si, Fe and Zn on the PHB matrix without peaks for other impurities, and dynamic light scattering confirms the excellent stability of nanocomposites in the solution. TEM micrographs confirm that the nanocarriers have different morphologies (spherical and nonspherical). ART@Scell-g-PHB-10%DA@Fe3O4/ZnO showed unique and powerful activity against S. aureus, E. coli, K. pneumoniae, and Pseudomonas P. aeruginosa compared with Pcell-g-PHB-10.0% Fe3O4/ZnO, and Ccell-g-PHB-10.0% Fe3O4/ZnO. However, ART@Pcell-g-PHB-10.0% DA@Fe3O4/ZnO showed the highest efficacy against the HCT-116 cell line (IC50 = 12.3). These results confirm that ART@Scell-g-PHB-10.0% DA@Fe3O4/ZnO, and ART@Pcell-g-PHB-10.0% DA@Fe3O4/ZnO might be a promising drug delivery system for efficient prolonged drug release, and targeting the tumor cells. Part III: In this work, Polyhydroxybyturate copolymer chitosan (PHB-Co-CS) were synthesized by a coupling reaction between PHB-diol and CS-diisocyanate, with different molecular weight of CS. Stannous octanoate was used as catalyst. ART/CUR@PHB-Co-LCS, ART/CUR@PHB-Co-HCS, ART@ PHB-Co-LCS-CUR@Fe3O4/ZnO, and ART@PHB-Co-HCS-CUR@Fe3O4/ZnO were formulated by solvent evaporation from oil-in-water single emulsion method. The XRD and FTIR techniques have shown that the formation and coupling reaction occurred between PHB and CS polymers. Zeta potential of ART/CUR@PHB-Co-LCS, ART/CUR@PHB-Co-HCS, ART@ PHB-Co-LCS–CUR@Fe3O4/ZnO, and ART@PHB-Co-HCS-CUR@ Fe3O4/ZnO were found to be 4.3 0.51, 6.13 ± 1.03, 2.71 ±0 .19 and 3.03 ± 0.156, respectively. The release rate of the ART/CUR drugs from the prepared carriers-loaded ART/CUR with respect to the effect of the molecular weight of polymer and the percentage of loaded drug was studied by immersing in buffer solution with different pH values (pH 5.4 and 7.4). The molecular weight of CS in PHB NPS control the encapsulation efficiency of the ART. The loading percentage ART/CUR on PHB-Co-LCS copolymer, PHB-Co-HCS copolymer was calculated to be 70.0, and 89.0 %, for ART and 86.7 and 66.0 % for CUR, respectively. The loading % of ART on PHB-Co-LCS– CUR@Fe3O4/ZnO, and PHB-Co-HCS-CUR@Fe3O4/ZnO NCs was calculated to be 56.0, and 72.0 % respectively. The antibacterial efficacy of the ART/CUR loaded PHB-Co-LCS copolymer revealed significant activity compared to PHB-Co-HCS copolymer, PHB-Co-LCS/ Fe3O4/ZnO NC, and PHB-Co-HCS/Fe3O4/ZnO NC for E. coli (Gram negative) and S.aureus (Gram positive). The highest antitumor activity against the tested tumor cell line was displayed ART/CUR@PHB-Co-LCS, ART/CUR@PHB-Co-HCS, and IC50 was recorded to be 8.09± 0.7 and 11.89 ± 0.9 μg mL−1, respectively, reflecting the very strong cytotoxicity against the HCT-116 tumor cell lines.