Preparation and characterization of hybrid nanomaterial containing magnetic Fe3O4 nanoparticles as drug delivery systems

Cancer is one of the most common and deadly health problems in the world. Doxorubicin is a cytotoxic drug used in chemotherapy. It causes actively growing cells, such as cancer cells, to slow or stop growing, and increases the likelihood that these cells will die. Paclitaxel demonstrates its antitumor effect by increasing the collection of microtubules in the cell and preventing their depolymerization by forming stable microtubule communities. The combination of paclitaxel and doxorubicin is widely used in the treatment of cancer types. Combination chemotherapy of drugs with different anti-tumor mechanisms is a useful way to reduce drug resistance and improve therapeutic effect. However, the combination of free pacsitaxel and doxorubicin causes severe toxicity in normal tissues, such as cardiotoxicity and neurotoxicity. Therefore, it is necessary to develop a highly effective and low toxicity formulation or formulations of the two drugs. In this thesis, magnetic Fe3O4 nanoparticles were synthesized and the magnetic surfaces of the nanoparticles were modified with thiol groups. The chitosan polymer, which was then modified with allyl groups, was prepared and bound to magnetic nanoparticles by the click reaction. The drugs paclitaxel and doxorubicin were loaded separately and together into this prepared hybrid material, and then drug releases from the hybrid material were studied. Structure characterization for all steps of surface modification of Fe3O4 was done with ATR-FTIR. It has also been characterized by Zeta sizer size analyses of magnetic nanoparticles, thiol-modified magnetic nanoparticles, and polymer-bound magnetic nanoparticles. Structural characterizations of allyl modified polymers were determined by ATR-FTIR and NMR. TGA analysis was used for thermal strength and percentage modification of hybrid nano material. In the thesis study, it was determined that chitosan-Fe3O4 nanoparticles were loaded with 255.17 µg doxorubicin and 287.17 µg paclitaxel. When both drugs were treated together with chitosan-Fe3O4 nanoparticles, 253.2 µg DOX and 274.7 µg PTX were found to be loaded. From chitosan-Fe3O4 nanoparticles, doxorubicin was found to be released 30.5% at pH 5 and 23.3% at pH 7.4 at 48 hours. Paclitaxel was released at 48 hours by 72.66% at pH 5 and 41.45% at pH 7.4. Doxorubicin and paclitaxel drug releases loaded together into chitosan-Fe3O4 nanoparticles were examined at pH 5 and pH 7.4 and it was determined that both drugs were highly released at acidic pH and that the release was completed in 48 hours. The release of anticancer drugs such as doxorubicin and paclitaxel in the body has been reported to be greater in slightly acidic tumor microenvironment and acidic environments in intracellular tumor cells. In our study, it was found that the release of both drugs separately and together was higher in an acidic medium.