Akademik Veri Yönetim Sistemi
Tezin Türü: Yüksek Lisans
Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Bilimleri Enstitüsü, Fen Bilimleri Enstitüsü, Türkiye
Tezin Onay Tarihi: 2017
Öğrenci: ESRA METİN
Eş Danışman: PELİN MUTLU, UFUK GÜNDÜZ
Özet:Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells also effect as cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks.The targeting strategy can be changed depending on carrier types, but magnetic nanoparticles are commonly preferred due to their easy targetable features by using external magnetic field. In this study, poly(dl-lactic-co-glycolic acid) (PLGA) coated magnetic nanoparticles were synthesized for targeted co-delivery of doxorubicin and vitamin E TPGS to breast cancer cells. TPGS is known as an inhibitor of multidrug resistance, enhancer of cellular drug uptake and drug release rate. The magnetic nanoparticles were synthesized by coprecipitation method, and then coated with oleic acid. Coated nanoparticles were encapsulated in PLGA and TPGS polymer and drug loaded form of this polymeric magnetic nanoparticle was also produced. vi Synthesized nanoparticles were characterized by using FTIR, zeta-potential, XPS, VSM, DLS, TGA, SEM, TEM and spectrophotometric analyses. The results showed that the nanoparticles were spherical, superparamagnetic and drug loaded nanoparticle (NP) size was 121 nm which is in the range for successful targeting. Moreover, TPGS and doxorubicin loading were confirmed by TGA and FTIR analysis. Drug loading and release profiles were studied. It was found that 177 µg doxorubicin was loaded on 1 mg Dox-PLGA-TPGS-MNP (Dox NPT20) nanoparticle and 155 µg on Dox PLGA-MNP (Dox NPT0). In both types of nanoparticles, a sustained release profile was obtained. Internalization of magnetic polymeric nanoparticles was detected by Prussian blue staining technique. The NPs were taken by cells in 5 hours. Presence of TPGS on core material increased the cellular internalization of nanoparticles in human breast adenocarcinoma cell lines (drug sensitive MCF-7 and doxorubicin resistant MCF-7/Dox cells). Moreover, the targetable properties of magnetic polymeric nanoparticles were shown by applying an external magnetic field. XTT cell proliferation assay indicated that drug free nanoparticles did not killed the cells (MCF-7 and MCF-7/Dox) and the cytotoxic effects of drug loaded nanoparticles on drug sensitive and drug resistant cell lines were shown. The cytotoxic effects of drug loaded nanoparticles increased in the presence of TPGS in core. In addition, TPGS increased the drug accumulation in drug resistant cells. Doxorubicin and TPGS loaded magnetic polymeric nanoparticles due to their size, biocompatibility, cytotoxicity and targetable properties could be used in new generation targeted chemotherapy.