Encapsulation and characterization of chemotherapeutic l-asparaginase with artificial red blood cells

Master Thesis ENCAPSULATION AND CHARACTERIZATION OF CHEMOTHERAPEUTIC L-ASPARAGINASE WITH ARTIFICIAL RED BLOOD CELLS Gülşah KARADÖL İnönü University Graduate School of Natural and Applied Sciences Chemistry Department 63+xi 2019 Supervisor: Prof. Dr. Burhan ATEŞ L-asparaginase (L-ASNase) is the primary chemotherapeutic drug used in the treatment of Acute Lymphoblastic Leukemia (ALL). Currently, L-ASNase is applied modified with polyethylene glycol (PEG). One of the most important problems in this practice is the side effect caused by the immune response developed by the body. Therefore, novel L-asparaginase delivery systems are needed to solve such problems in the treatment of ALL. The aim of this study is to develop a carrier system for L-asparaginase from artificial red blood cells. Within the scope of the thesis, oleic acid (OA) was firstly grafted to starch (ST) in the presence of tween 40. Subsequently, artificial red blood cell systems were established in the presence of hemoglobin and L-asparaginase. Each step of the obtained systems is characterized structurally, thermally and morphologically. Also, particle size, zeta potential and L-asparaginase activity, pH and temperature stability, reusability and storage stability of this system were investigated. The average hydrodynamic particle sizes of the OA / ST and OA/ST-Hb-L-ASNase materials were measured as 120 and 295 nm, respectively. OA / ST-Hb-L-ASNase maintained more than 60% of its relative activity at 55 ° C. After one week, the remaining activity was 59% for the free enzyme and 68% for the immobilized enzyme. Furthermore, OA/ST-Hb-L-ASNase maintained approximately 50% of the initial activity even after repeated use of 15th. As a result, promising results were obtained for the use of artificial red blood cells in transporting L-asparaginase enzyme. Key Words: Artificial red blood cell L-asparaginase, starch, oleic acid