Doxorubicin loaded melanin nanoparticles for breast cancer therapy

According to 2014 data, breast cancer is the most common cancer in women in Turkey. One out of every 4 women diagnosed with breast cancer. Currently available clinical procedures are surgery, chemotherapy, radiation therapy, hormone therapy and targeted therapy. Doxorubicin is an efficient chemotherapy drug usually used in breast cancer therapy. Dose dependent toxicity, drug resistance and low selectivity to cancer cells limit the use of doxorubicin in clinical practice. Nanotechnology is the leading approach to eliminate these disadvantages. Developments in nanotechnology have a significant impact on drug delivery systems. Nano-sized drug delivery systems provides controlled release of drug, chemical stability, surface modifications, therefore they protect the drug from the immune system and prolong the half-life of the drug, increase bioavailability, reduce possible side effects and broaden the therapeutic window. Nanoparticles play an important role as a drug delivery system in many clinical applications and researches. Nanoparticle platforms include: liposomes, micelles, dendrimers, albumin based and polysaccharide based nanoparticles, metal, ceramic and polymeric nanoparticles. Melanin is a biopolymer with good biocompatibility and biocompatibility, intrinsic photoacoustic properties and it can also bind to drugs and chelate with metal ions. Within the scope of this thesis; i) synthesis of melanin nanoparticles, ii) modification of melanin nanoparticles with polyethylene glycol, iii) loading of doxorubicin drug to polyethylene glycol modified melanin nanoparticles and iv) examining the release profile, v) in vitro cytotoxicity assay for the proposed drug delivery system were performed. Morphology, chemical structure, surface charge and light absorption properties of synthesized nanoparticles were investigated with transmission electron microscope (TEM), Fourier transformed infrared (FT-IR), zeta potential analyzer, ultraviolet and visible light (UV-Vis) absorption spectroscopy, respectively. The drug loading capacity and drug release profile of the nanoparticles were analyzed using the UV-vis spectrophotometer device. Cell viability was evaluated by employing the MTT viability assay. Results showed that melanin nanoparticles (MNP), PEG modified melanin nanoparticles (PEG-MNP) and doxorubicin loaded melanin nanoparticles (DOX-PEG-MNP) have spherical shape with the size of 50, 30, and 15 nm and their surface charge were -24, -22 and -40 mV respectively. DOX-PEG-MNP system provides controlled release of drug. In vitro cytotoxicity assays showed that MNP and PEG-MNP did not show any toxic effect on healthy cells while DOX-PEG-MNP was able to kill breast cancer cells effectively. In this thesis, it is suggested that doxorubicin loaded melanin nanoparticles can be effectively used as drug delivery systems in biomedical engineering approaches. Keywords: Melanin, Doxorubicin, Nanoparticle, Drug delivery systems, Controlled drug release.