الفهرس 
Introduction Aim of the workOnly 14 pages are availabe for public view
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Abstract
The present study explored the fabrication of PMMA-PHP complex nanofibrous scaffolds as a novel model of biomaterials possessing anti-cancer properties. PHP (PVP: H2O2) complex was used as a source of oxygen, which as was confirmed previously the role of oxygen in cancer treatment. On the other hand, sandwich configuration models of 6-MP loaded PMMA/PCL nanofibrous mats were fabricated by electrospinning technique and extensively evaluated for their efficiency in enhancing the drug properties, controlled drug release, and inhibition of the cancer cells. Thesis content: Content of the thesis is ( 5 ) chapters as follow: Chapter one: Introduction and Aim of the work Globally, cancer is the second cause of death with an estimated more than 9.6 million deaths in the year 2020 according to studies conducted by the World Health Organization. Nearly three-quarters of cancer deaths occur in middle and low-income countries. Most solid tumors develop due to hypoxia when the normal cells suffering from an insufficient oxygen supply are converted to cancer cells. Recent studies demonstrated that tumor hypoxia is a critical obstacle to effective cancer treatment with chemotherapy, immunotherapy, as well as radiotherapy. However, conventional chemotherapeutic agents are insufficient due to their negative features, so our study aims to innovate a new model for treating tumors using oxygen and 6-MP loaded nanofibers scaffolds. Chapter two: Review of Literature Many studies say that most solid tumors develop due to a lack of oxygen, as normal cells that suffer from a lack of oxygen are converted into cancerous cells. It has been demonstrated that patients exposed to hyperbaric oxygen (HBO) immediately before irradiation show a significant improvement in the efficacy of radiotherapy and that oxygen increases the susceptibility of cancer cells to chemotherapy. Therefore, various sources of oxygen are being explored, such as oxygen-releasing biomaterials e.g. solid inorganic peroxides like sodium percarbonate, calcium peroxide, magnesium peroxide, and liquid peroxide as hydrogen peroxide in attempts to reverse hypoxia occurring. Here, Hydrogen peroxide was complexed with polyvinyl pyrrolidone (PVP) to create PHP complex (PVP-hydrogen peroxide) to increase its stability and provide a sustainable manner of oxygen. 6-Mercaptopurine (6-MP) is a well-known commercial drug as an anti-cancer agent, immune suppressant, and treatment of inflammatory diseases. 6-MP goes through complex biotransformation representing the drug inactive. Therefore, 6-MP suffers from limiting their bioavailability by increasingly prescribed to destroy by thiopurine S methyltransferase and Xanthine oxidase. So this might lead to a decrease in its bioavailability by approximately 16%. In particular, we provide the first demonstration of blending 6-MP into sandwich electrospun PCL/PMMA nanofibrous scaffold as an anticancer platform. The results present the physicochemical properties of different composite mats, their biocompatibility, anti-microbial activity, cytotoxicity, and finally their potential as a novel efficient sustained drug-releasing biomaterial for cancer treatment. Chapter three: Materials and Methods In this study, an electrospinning technique was used to synthesize all the nano-scaffolds loaded with oxygen and 6-MP from PMMA & PCL polymer. Moreover, the release of oxygen and drug was controlled gradually. The physical and chemical properties of the electrospun nanofibrous scaffolds as well as the evaluation of biocompatibility, cytotoxicity, antimicrobial activity, anti-cancer properties, and finally their potential as a novel oxygen-releasing biomaterial and loaded with the anti-cancer drug were determined. Chapter four: Results The PHP complex (PVP: H2O2) was used as the oxygen source and it was noted that the scaffold that releases oxygen gradually and continuously is PMMA + 10% PHP due to distribution of the PHP complex in a good way and it also showed the highest mechanical properties with smooth nanofibers. A dose (1 mg/ml) of nanofibers showed an intense reduction of different tumor cells, with results confirming cell breakdown to 30%; However, the same dose revealed a very safe behavior on the healthy cell. We also fabricated 6-MP-loaded PMMA/PCL tri-layered (sandwich) nanofibrous scaffolds using electrospinning technology and evaluated them extensively for their drug-release efficiency. The results also demonstrated success in controlling the initial dispersion of the drug and the continuation of drug release for more than 21 days, which led to a reduction in its toxicity on normal cells. The effect of manufactured scaffolds on various cancer cells in vitro such as colon cancer cells, liver cancer cells, and breast cancer cells was also studied. The results showed that the cancer cells decreased to approximately 12% by using the scaffold consisting of (2% PCL/ 4% PMMA/ 1% 6-MP). Chapter five: Conclusion According to our findings, the use of PMMA-PHP oxygen-synthesized nanofibrous scaffolds in addition to 6-MP drug-loaded nanofibers (2% PCL/ 4% PMMA/ 1% 6-MP) are recommended as possible biomaterials for cancer therapy.