الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Lung cancer is the most commonly diagnosed worldwide, and causes more deaths than any other cancer. Current cancer therapy protocols usually involve surgery followed by radiotherapy and chemotherapy. Chemotherapy provides a small improvement due to the cytotoxicity of anticancer drugs (among which methotrexate) and severe side effects often exerted by anticancer drugs.
Therefore safer, more effective, and site-specific alternatives are needed. Biodegradable and biocompatible polymeric nanoparticles have been developed as potential drug delivery systems. Nanoparticles remain in the blood circulation for a longer time and can passively accumulate at target tumor sites after systemic administration because of their leaky vasculature and poorly developed lymphatic drainage.
This accumulation reduces systemic toxicity by reducing damage to normal cells and increases the therapeutic benefits. The aim of this study was to develop Poly (lactic-co-glycolic acid) nanoparticles as a carrier for methotrexate and evaluate their efficacy as inhalation therapy in lung cancer therapy. This work is divided into two chapters. Chapter one: Formulation and in vitro evaluation of methotrexate polymeric nanoparticles intended for lung cancer The first chapter of the thesis aims at formulating polymeric nanoparticles based on poly (lacticco-glycolic acid).
Several preliminary experiments were conducted to study the influence of formulation parameters for the particle preparation using solvent evaporation technique. For optimizing the NPs formulation, ethyl acetate, dimethyl sulfoxide and dichloromethane were tested as an organic solvent in different ratios and concentration in relation to the aqueous medium.
The concentration of stabilizer (polyvinyl alcohol), the homogenizer speed and time were varied. Physiochemical properties of polymeric nanoparticles such as morphology, size, zeta potential, entrapment efficiency, in vitro drug release and cytotoxicity were investigated.
Also, the suitability of nanoparticle to be delivered to the lungs by nebulization therapy was evaluated. The results showed that the nanoparticle size ranged from 184 to 472 nm with negative zeta potential ranging from -17 to -30 mV.
The entrapment efficiency also varied and the maximum value was 48.76%. The stability study revealed that the nanoparticles was stable up to 120 days at 4 ºC. The release profile exhibited sustained release effect up to day 14. The viability test experiment showed that the nanoparticles formed were active against adenocarcinoma lung cells having lower toxicity than the free MTX. The nanoparticles revealed physical stability against forces generated during aerosolization, which could be attributed to the adsorbed PVA layer around the nanoparticles.