Research Of Compound Vincristine Liposomes Against Cancer

Cancer is not only a common but also the most dangerous disease to human health. According to statistical research, about nine million people catch cancer and seven million cancer patients die each year around the world. Although surgical operation, radiation therapy, chemotherapy and biomedical therapy are the main methods for the treatment of cancer at present, their efficiency is limited. In order to find an efficient way for cancer treatment, people had done a lot of work. In the early days, doctors use one anticancer drug in the chemotherapy of cancer, but take only one anticancer drug lead to low cure rate and drug resistance. Recently, doctors came to know that compared with single drug, combined chemotherapy increase cytotoxic efficacy of drugs, attack different biochemical targets, work with different mechanisms: additive or synergistic, work at different phases of cell cycles, over come drug resistance, non-overlapping toxicities. So combination chemotherapy is the most widely used method for cancer treatment now.Mitoxantrone and vincristine are two popular anticancer drugs in clinical use. They work at different phases of cell cycles and by different mechanisms. They have been used in combination in the treatment of mammary cancer, acute lymphocytic leukemia, non-Hodgkin's lymphoma and myeloma.In this research, liposomes were used as the two anticancer drugs carriers in order to improve cure rate of cancer and to decrease side-effects. These innovative studies below-mentioned were not yet reported.As a kind of drug carrier, liposomes may be very promising because of its biodegradability, lack of toxicity and antigenicity and controllable drug-release properties. Liposomes with small particle size(~50nm) showed prolonged drug resident time in blood circulation system and reduced drug uptake by the reticuloendothelial system simultaneously.The liposomes loaded with MTO and VCR were prepared by PH-gradients method. Laser particle analyzer was applied to determine the particle size and zeta potential of the liposomes. The mean diameter of the liposomes loaded withMTO and VCR was 76.61nm and its zeta potential was -30.97mv. The entrapping efficiency is 99.53%±0.34% (n=3) for MTO and 95.77%±2.70% (n=3) for VCR. The drug loading is 2.5%±0.10% (n=3) for MTO and 0.38%±0.O5% (n=3) for VCR. Observed with transmission electron microscope, liposomes had good spherical shape.The HPLC methods were established for determination of the MTO and VCR in MTO-VCR-LP and in biological material.Mice tail intravenous injection of MTO-VCR-LP showed that compared to MTO-VCR-Soln, MTO-VCR-LP prolonged the resident time and improved the concentration of MTO and VCR in the blood circulation system. In the same time, MTO-VCR-LP reduced the concentration of the MTO and VCR in heart, lung, kindney etc. The results implied that MTO-VCR-LP could get higher cure rate of cancer and lower side-effect.The LD5O(95% confidence limit) of MTO-VCR-LP and MTO-VCR-Soln was 4.2 mg-kg''(2.9235~5.9428)and 2.7mg-kg"'(0.9798~ 7.4398) respectively.The mammary cancer model of Blab/c nude mice were made using MCF-7cells and divided into seven groups: control group, VCR-Soln, VCR-LP, MTO-Soln, MTO- LP, MTO-VCR-Soln and MTO-VCR-LP. After the first treatment in the same day of transplant, different treatment were given respectively. The Blab/c nude mice were undertook therapy as the plan and the weight of nude mice and tumor volume were weighed, the tumor growth inhibitory rate were calculated. The tumor growth inhibitory rate were higher in MTO-VCR-LP and MTO-VCR-Soln groups than other groups. The weight of nude mice among the three liposomes groups were higher than the three solution groups.In conclusion, using liposomes as the carriers of two anticancer drugs could improve the cure rate of cancer and decrease side-effects. Liposomes loaded with two anticancer drugs were first prepared in this research. MTO and VCR in MTO-VCR-LP and in biological material were determination by HPLC. Further study on drug distribution, acute toxicity and therapeutic effect against breast cancer were carried out. All these studies above-mentioned were not yet reported. A good theoretical and practical foundation was established for the exploration of the two drugs loaded liposomes' dosage formula, characteristics and work mechanism in this research, which not only enlarged research field of liposomes but also brought new ideas and new methods to treat cancer. Further more, this research has potential value in clinic practise.