Synthesis and characterization of polymeric magnetic nanoparticles loaded by gemcitabine


Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Bilimleri Enstitüsü, Fen Bilimleri Enstitüsü, Türkiye

Tezin Onay Tarihi: 2014

Öğrenci: MARYAM PARSIAN

Danışman: UFUK GÜNDÜZ

Özet:

In this study, different types of magnetic nanoparticles were synthesized for treatment of breast cancer by targeted drug delivery. Polyamidoamine (PAMAM) dendrimer, Chitosan (CS) and Polyhydroxybutyrate (PHB) coated magnetic nanoparticles were prepared and loaded with Gemcitabine. The loading efficiency of drug for various half generations of dendrimer coated magnetic nanoparticles (DcMNPs), Chitosan coated magnetic nanoparticles (CSMNPs) and Polyhydroxybutyrate magnetic nanoparticles (PHB-MNPs) were investigated in different solvents. The results were confirmed by spectrophotometric, FT-IR, XPS, Zeta-potential and TEM analyses. The release and stability of Gemcitabine from the nanoparticles at various pH were investigated. The release studies were shown Gemcitabine release was higher at pH 4.2 compared to pH 5.2. The stability results indicated that Gemcitabine conjugated nanoparticles were highly stable. The cytotoxicities of drug free nanoparticles and Gemcitabine loaded nanoparticles were determined with proliferation assays (XTT) using SKBR-3 and MCF-7 cell lines. DcMNPs, CSMNPs and PHB-MNPs were not cytotoxic by themselves. When the drug was loaded on DCMNPs, CSMNPs and PHB-MNPs, the antiproliferative effect of the drug increased. IC50 values of drugs remarkably decreased 6, 1.4 and 2 folds on SKBR-3 and 3, 2.6 and 2 folds on MCF-7 cell lines, when conjugated to DcMNPs, CSMNPs and PHB-MNPs, respectively. Considering the fact that the synthesized bare magnetic nanoparticles were not cytotoxic and Gemcitabine loaded nanoparticles exhibited higher antiproliferative activity than free drug in vitro, we suggested that these nanoparticles can be a promising candidate for the development of novel targeted drug delivery systems.