Meme Kanseri Tedavisinde Kontrollü İlaç Taşınım Sistemi Olarak Lipit Nanotüplerin Kullanım Potansiyelinin İncelenmesi

Abstract

Breast cancer is one of the leading cancer types which gives rise to death. Chemotherapy is still the most preferred way of the treatment with the radiation and surgery yet the chemotherapeutics can cause serious organ damage. Therefore, working with anticancer agents has various risks. For addressing main obstacles in the cancer therapies and to improve their therapeutic efficacy, drug delivery systems (DDS) based on nanotechnology have become a promising alternative over the conventional therapies. Lipid nanotubes (LNTs) are open-ended, hollow cylindrical nanocarriers that consists of amphiphilic monomeric units and owing to these monomers LNTs could be formed by self-assembly method in aqueous media. LNTs have different advantages such as biocompatible membrane surface and tubular geometry with tunable dimensions. All these characteristic features make the LNTs favourable candidates for drug delivery. The selected model anticancer agent mitoxantrone (MTX) is a well-known synthetic anthracenedione antibiotic which is commonly used for treatment of breast cancer, prostate cancers and leukaemia. The aim of this study is to develop a DDS for the treatment of breast cancer which is able to target the tumor side actively. It is also aimed to use the developed DDS in combination therapy in order to overcome the multi-drug resistance (MDR) and to take advantage of drugs synergistic cytotoxic activity. In order to achieve these aims, Aqua LNTs are decided to be used as nanocarriers because of their specially designed structure gives them a pH sensitive character which is the most preferred stimuli for the delivery of anticancer agents. In the second part, doxorubicin (DOX) is also added to system to investigate the potential use of Aqua LNTs as multiple chemotherapeutics carrier. MTX and DOX have been loaded to the Aqua LNTs via both electrostatic and π-π stacking interactions. In the drug encapsulation and release experiments, the analysis has been performed by using UV-vis spectrophotometry. Layer-by-Layer (LbL) technique which is develop via electrostatic interactions between the oppositely charged functional groups is preferred as a simpler and cost-effective strategy for the functionalization of Aqua LNTs. LbL technique not only reduce the initial burst release but also makes a contribution to molecular targeting strategies if the layers are composed of different ligands. In these studies, alginate (ALG) has been used as first coating layer. Also, folic acid (FA) has been selected as targeting ligand due to its presence on the breast cancer cell membrane and it has been introduced to Aqua LNTs after conjugation with chitosan (CHI) chemically. In order to characterize the Aqua LNTs which are coated by ALG or FACHI layers, Atomic Force Microscopy and zeta potential measurements were performed. As a conclusion, MTX loading was achieved to Aqua LNTs with 90% encapsulation efficiency and the release period was reached to 168 hours after LbL coating.