The Experimental Study Of The Effect Of Temozolomide Nanometer Sustained-release Microsphere On Rat Glioma Model

Objective:To study the releasing rules of TMZ-PLGA sustained-release microsphere in vivo and reproduce the relatively stable C6/Wistar rat glioma model.To Calculate the tumor formation rate and analyze imaging characteristics through Magnetic resonance imaging.To analyze the effect on lifetime of tumor-bearing rats of TMZ-PLGA-MS and observe the changes of the imaging and tumor pathology.Methods:TMZ-PLGA-MS of 7.5% drug loading were implanted in rat’s brain and taken out in different time.The rest of the TMZ’s content in the tablets were Calculated by high pressure liquid chromatograph and the intracranial release curve were drawn.C6 glioma cells were Implant into the right caudate nucleus of rats by stereotaxic instrument and stable glioma model were reproduced.To calculate the tumor formation rate and analyze imaging characteristics through Magnetic resonance imaging. C6/wistar glioma models were divided into five groups randomly:TMZ-PLGA-MS implanting group (T1), TMZ implanting group (T2), PLGA implanting group (T3), TMZ oral group (T4) and blank group (T5).There were 10 rats in each group.MRI scans were performed again at the 16th day and tumors volume was calculated. Pathological examination Pathological examination was studied from two random samples of each group.The remaining eight rats of each group were used to observe and analyze the survival.Results:High pressure liquid chromatography was used for calculating releasing rules of TMZ-PLGA-MS in vivo.The releasing time was more than 14 days.There were 52 rats showing the abnormal signal in the right caudate nucleus head by the MRI scans and the tumor formation rate was 86.7%. The imagings showed irregular abnormal signal on the right caudate nucleus head, low signal on T1 WI、high signal on T2WI and enhanced signal.The five groups’ tumor volume were analyzed with ANOVAT. The tumor volumes in group T1 had statistically difference compared with other groups. There were statistically difference between Group T2 and group T5,group T4 and group T5.PCNA and Ki-67 staining displayed brown tumor cell nucleus.FⅧ-Rag staining displayed brown endothelial cells.The PI of Group T1 had statistically difference compared with other groups.The median survival times of group T1 to T5 were 35、 26.5、26、27.5and 23.5days.The survival rates of each group had statistically difference.Conclusion:Implanting C6 glioma cells in head caudate nucleus of wistar could get stable animal glioma model and the tumor formation rate was completely satisfied for present experiment. It was applicable to observe imaging of rat glioma model through MRI that showed intuitive and believable images. High pressure liquid chromatography could be used for calculating releasing rules of TMZ-PLGA-MS in rats’ brain and The releasing time was more than 14 days that met the requirements of local interstitial slow-release drug medication.3.0 TMRI and 3Dslicer technology could be used for calculating C6/wistar rat glioma volume. TMZ-PLGA-MS had more significantly effect on tumor growing,reducing PCNA index and prolonging the survival period than that of the other groups.It illustrated that TMZ-PLGA Nanometer Sustained-release Microsphere had great effect on intracranial C6/wistar rat glioma.