Study On Tat Folate Mediated Magnetic Multi-functional Delivery System

In this paper the preparation of O-carboxymethylated chitosan coated superparama- gnetic nanoparticles using chymistry co-precipitation method is introduced. We also discuss the preparation of condition of Fe304 magnetic fluid. And the appearance, size, surface electric charge characteristic and the crystal structure of the carrier are charac- terized by using TEM, IR, Particle Size Analyzer, Zeta Potential Analyzer, Vibrating Samples Magnetometer, X-ray diffraction and X-ray photoelectron spectrum.In this study, we found the optimum conditions for synthesizing O-carboxymethylated chitosan superparamagnetic nanoparticles. The results showed that the average sizes of all the carriers which were coated with O-carboxymethylated chitosan are about 100nm and still retained well-shaped morphology with narrow size distribution and magnetic properties that are close to suerparamagnetic matters. The X-ray diffraction investigate the crystal structure of samples were Fe3O4.Then these O-CMC-MNPS were surface functionalised by Folic acid (FA) and Tat oligopeptide so that the O-CMC-MNPS had multi-functions including active targeting , physical/magnetic targeting transducation for the blood-brain barrier(BBB). The quantities of both FA and Tat on O-CMC-MNPS were tested by adopting dispersion method.The biodistribution of surface functionalised O-CMC-MNPS in brain, heart&lung, liver&spleen, kidney and bladder of SD normal rats was investigated by 99Tc-labeled SPECT. The functions of Folic acid, Tat and effect of action time of magnetic field had also been further investigated.Drug delivery systems carrying Sodium Valproate(SVP), called Tat-FA-O-CMC-MNPS, had been prepared successfully. The biodistribution proved they were successfully passed the blood-brain barrier under the magnetic field, and the brain distributing was much higher than other groups.The epileptic animal seizure modal had been established , and SD modal rats were 18 cases were divided randomly into 3 groups, Physiological Saline and Sodium Valproate(SVP) were performed in group 1 and 2 respectively, and Tat-FA- O-CMC-MNPS was used in group 3. The results of electroencephalograph, apoptosis test and Immunophenotype test had proved that the therapeutic efficiency of Tat-FA- O-CMC-MNPS were much better than that of Physiological Saline and Sodium Valproate(SVP).In sum, Magnetic multi-functional delivery system could be applied in the gene/drug therapy of brain diseases which need cross the blood-brain barrier(BBB).