چكيده به لاتين
Since a long time ago drug delivery science with the goal of reducing the drug side effects and controlled release of drugs is working to design an effective drug delivery system. These systems have revolutionized the treatment of many diseases, especially cancer. The goal of this project is to achieve a biocompatible, biodegradable, pH-sensitive drug delivery system with a higher release in acidic environments, controlled and prolong release for the cancer treatment. For this purpose, chitosan nanoparticles were synthesized by simple, mild and green ionic gelation method with tripolyphosphate as the crosslinking agent. Synthesized chitosan nanoparticles have a uniform spherical morphology with a size range of 20-35 nm and positive surface charge. Doxorubicin, one of the most widely used anticancer drugs, was loaded onto chitosan nanoparticles. In order to increase the encapsulation efficiency, the effect of different parameters was studied and the optimal values with an encapsulation efficiency of %81.6 were obtained. The release of the drug from chitosan nanoparticles was studied at pH: 4.5, 5.5, 6.5 and 7.4 for 28 days. Single-layer or few-layer graphene was synthesized by a simple and green method by probe sonicator and was characterized by uv-vis spectroscopy and atomic force microscopy. For the first time, a new nanocomposite of chitosan nanoparticles and graphene was synthesized in three different weight percent of graphene based on the electrostatic interaction between chitosan nanoparticles and graphene, and its release curve was compared with the release curve of chitosan nanoparticles. The addition of graphene to chitosan nanoparticles leads to more controlled release and reduces the burst release of the drug compared to chitosan nanoparticles. By investigating the release curve and cytotoxicity by MTT assay, optimal weight percent of graphene was determined. Also, the mechanism of drug release from chitosan nanoparticles and optimum nanocomposite was evaluated by examining different models. Finally, the effect of the nanocomposite in the treatment of SKBR-3 cancer spheroids was investigated in order to compare the experimental results with in vivo results.
