Study On Oxaliplatin Long-circulating Thermosensitive Liposomes

At present, cancer is one of serious diseases threatening the life of human. People treat cancer by a number of ways. The drug therapy has an irreplaceable position. However, most of anticancer agents are utilized limitedly in clinic because of the side effects. Oxaliplatin is one of the most effective anticancer drugs available in clinic currently. However, it has some toxicity and was limited its application. Liposome is one of the significant progresses in tumor treatment. Because it can increase therapeutic effect, reduce toxicity. Liposomal antineoplastic agent is characterized by delayed-releasing and tumor targeting. Long-circulating thermosensitive liposome (LTL) is a new kind of liposome. When anticancer drugs are encapsulated in LTL, not only decrease the clearance of RES and prolong the circulating time, but also increase the drugs release quickly at the tumor site. In this study, we selected Oxaliplatin (Ox) as the model drug, and prepared the Oxaliplatin long-circulating thermo-sensitive liposome (OLTL). Expect of increasing the therapeutic effect of Oxaliplatin and reducing the side effects.In this study, OLTL was prepared by thin film hydration method. The formulation design and preparation process of OLTL were studied and evaluated with particle size distribution and encapsulation efficiency. The optimized formulation was scaled-up, in order to determine preparation process of industrialization. The particle size and encapsulation efficiency of the liposome was 154.83±2.33nm and above 90%. The physico-chemical property of OLTL was studied including appearance, pH, the stability and thermosensitive feature in vitro. The release behavior of the drug from liposomes was studied by dialysis method. In 6 hours, The release ratio of OLTL in vitro was more than 90% at 42℃. The stability of dilution and filtration were fine. OLTL remained stable at different temperature. The HPLC method was established to determine the Oxaliplatin concentration and encapsulation efficiency of OLTL. The Lewis lung cancer model mice was established by i.v. immunosuppressant. The anti-tumor activity of OLTL was evaluated. The rate of tumor inhibition was 70.79%. OLTL has a significant difference compared to the control groups.The preparation technique in this study was stable and repeatable. OLTL was a temperature-sensitive remarkably and stability. The HPLC method was established to determine the Oxaliplatin concentration and encapsulation efficiency of OLTL. The research of pharmacodynamics demonstrated that OLTL could improve tumor inhibition efficacy.