Preparation Of The Released Microspheres Based On C60-Phe-PLA And Preliminary Study In Vivo Pharamcodynamic

Because of its unique physical and chemical properties，Fullerene(C60) has beenthe hot topic in the last decade. C60-phe, as the derivative of C60, has a good watersolubility and biocompatibility. And after the light irradiation, it can generate activeoxygen, thereby phototherapy can cure the tumor. Mitoxantrone(MTX) is ananthraquinone drugs, because that it does not have the structure of the amino sugar, itdoes not produce the free radicals and inhibit lipid peroxidation, inhibit lipidperoxidation, so it is lower cardiotoxicity.In this subject, we want to use the dispersion-solvent diffusion method toprepare mitoxantrone multifunctional microspheres, and Mitoxantrone as theanti-tumor model drug, the C60-Phe-PLA as the carrier material. This microspherecan combine the chemotherapy of the Mitoxantrone (MTX) and the phototherapy ofthe C60-Phe-PLA. And through the in vivo pharmacodynamic evaluation experiment,we evaluate the anti-tumor effect and the sustained release of the microsphere.The main content of this study include three parts:(1) the analysis of theprescription, which the C60-Phe-PLA is a carrier material;(2) the preparation andcharacterization of multifunctional microsphere;(3) the in vivo pharamacodynamicsevaluation of the multifunctional microspheres.1.the selection of model drug, which the C60-Phe-PLA is a carrier material.In this study, we use the dispersion-solvent diffusion method and theC60-Phe-PLA as the carrier material to prepare mitoxantrone,5-fluorouracil anddocetaxel microspheres, respectively. In this study, we use the orthogonal test tooptimize the prescriptions. After optimization the drug loading of mitoxantrone,5-fluorouracil and docetaxel is(8.090.15)%,(0.300.05)%,(4.720.23)%,respectively. Therefore, we finally chose the water-soluble model drug mitoxantrone.2. the preparation and characterization of multifunctional microsphereIn this study, we use the dispersion-solvent diffusion method to preparemicrospheres, which chose the mitoxantrone as a model drug and C60-Phe-PLA asthe multifunctional carrier. And the particle size, drug loading, in vitro release were used to characterize the microspheres. The results show that the particle size of themicrosphere distributed around8-20μm, drug loading is (8.090.15)%and in vitrorelease experiments show the multifunctional microspheres with sustained releaseproperties.3. in vivo pharmacodynamics evaluation of the multifunctional microspheres.According to the tissue distribution in C57BL mice, the MTX mainly spread inthe tumors, and in the heart, liver, spleen, lung, kidney there is almost no MTX.According to the pharmacodynamics experiment in C57BL mice, the tumorvolume of the group of treatment with MTX loaded microsphere/532nm laser issignificantly reduced.11days after injection, the T/C of the group of treatment withMTX loaded microsphere/532nm laser, the blank microsphere group/532nm laser, theblank microsphere without irradiating, MTX/532nm laser, MTX without irradiation is-7.38%、39.92%、140.07%、29.09%�'�29.11%, respectively. The results reveal thatMTX loaded microsphere after irradiation of the532nm laser has a better control ofthe B16-F10.The organ toxicity of the multifunctional microspheres reveals that MTX loadedmicrosphere/532nm laser almost has no organ toxicity.