Study On Preparation Of Brain-targeted BCNU Magnetic Nanospheres

Background and objective:Glioma is the most common malignant tumor in the central nervous system. Surgery plus radiotherapy and chemotherapy are effective, but patients have short survival, low quality of life and high rate of recurrence after operation. Carmustine is a regular chemotherapy agent for glioma. It's deemed to a golden standard for chemotherapy for glioma and always used to judge other chemotherapy agents. Carmustine has relative ability to cross the blood brain barrier as a result of fat-solubility and deionization. It's effectiveness is limited because of short half-time, ineffective concentration and duration and systematic complication such as delayed hematopoietic depression, cytotoxic effect on liver and pulmonary fibrosis. We want to develop carmustine magnetic nanospheres. With the effect of magnetic field, nanospheres can be carried to the targeted brain, raising the local concentration of drugs and reducing systematic side effect. We wish to propose a new method for glioma targeting therapy. Method:BCNU magnetic nanospheres were prepared through sonication emulsion evaporation. Entrapment efficiency was used as a main judgment of the quality of nanospheres. Determination of the optimal experimental conditions was based on orthogonal design. Ratio of BCNU/PLGA,concentration PLGA and PVA,sonication intensity were chosen as influential factors. Scan electron microscope was used to observe the shape of nanospheres. Mean diameter and distribution were also evaluated.In vitro release profiles were evaluated by high performance liquid chromatography. S-D rats were divided into three groups. The first group was given 100mg/Kg carmustine injection through caudal vein as the control. The second group was injected with BCNU magnetic nanospheres without magnetic filed at the same dose. The third group was given BCNU magnetic nanospheres with the effect of magnetic field. Brain tissues were collected to observe BCNU concentration 5min,15min,30min and 1h after injection respectively.Result:The optimal experimental design was A2B2C3D3.The most suitable condition was:the ratio of BCNU/PLGA wasl:7.5, PLGA concentration was 5%, PVA concentration is 3%, sonication intensity is 150W. Prepared nanospheres showed spherical surfaces. The range of mean diameters was from 50nm to 300nm. The mean drug loading rate was 4%. The mean entrapment efficiency is 32.2%. In vitro release profiles showed that after a short period of burst release, the magnetic nanospheres maintained a sustained release.15 minutes after injection, concentration of BCNU in non-magnetic field group and magnetic field group increased by 25% and 106% respectively, as compared with the control. The difference had a statistical significance.Conclusion:BCNU magnetic nanospheres prepared by sonication emulsion evaporation shows spherical surfaces. In the magnetic field, BCNU magnetic nanospheres can be used as brain-targeted chemotherapy for glioma due to its targeting characteristics and sustain release.