Poli (2-Hidroksietil Metakrilat) Aşılanmış Manyetik FE203 Nanoparçacıkların Sentezi ve Kontrollü Doksorubisin Salım Uygulaması

Abstract

The development of drug delivery systems is one of the most critical and challenging areas in modern medicine. Effective and targeted drug delivery can enhance treatment efficacy and reduce undesirable side effects, making the design and development of appropriate nanocarriers crucial. Magnetic nanoparticles can play an effective role as nanocarriers in cancer therapy due to their specific targeting capabilities. Surface modification of nanocarriers with various polymers tailored to the need may be necessary to enhance drug loading and release efficiency.

In this thesis, after the modification of magnetic Fe2O3 nanoparticles with poly(2-hydroxyethyl methacrylate) (pHEMA), nanocarriers loaded with doxorubicin exhibiting different release profiles depending on pH were synthesized, and controlled release studies were conducted. pHEMA was selected as the grafted polymer due to its low toxicity, high water solubility, and biocompatibility. The grafting of pHEMA onto magnetic nanoparticles relies on the redox activation exhibited by diazonium salts in the presence of a vinyl monomer and a reducing agent. Diazonium salts coat the surfaces with a thin layer similar to polyphenylene as a result of reduction processes triggered by the reducing agent. Aryl radicals formed during the redox reaction provide the necessary active functionalitiy for polymer chain grafting. This process, termed "Diazonium-induced Anchoring Process" (DIAP) or "GraftFast," was conducted under ultrasound processing to develop a green, rapid, and efficient grafting process in the thesis study. Adapting the ultrasonic polymerization method to the DIAP process is noteworthy as a relatively new approach in the literature.

The synthesized pHEMA-grafted Fe2O3 nanoparticles (pHEMA@Fe2O3) were characterized using FTIR, XPS, XRD, TGA, SEM, and TEM techniques. Characterization results confirmed the grafting of pHEMA onto Fe2O3 nanoparticles. The optimum ultrasound exposure time for synthesis was determined to be 10 minutes, and the optimum monomer/diazonium salt molar ratio was 10:1, as determined by FTIR and TGA results. The pHEMA-grafted magnetic nanoparticles, synthesized under optimal conditions, demonstrated an average loading capacity of 35.68% in a solution containing doxorubicin HCl (DOX) as a model drug, with an initial drug concentration of 0.5 mg/mL. Drug release behavior depending on pH was investigated in drug release studies conducted at different pH values using DOX-loaded pHEMA@Fe2O3 nanoparticles (DOX@pHEMA@Fe2O3), revealing that 87% of the loaded drug was released at pH 3, 46% at pH 5.5, and 37% at physiological pH 7.4. The results obtained within the scope of the thesis are important in terms of developing an innovative method for the modification of magnetic nanoparticles with polymers and controlled drug release, presenting a potential strategy for cancer treatment.