Preparation, Optimization And Evaluation Of Tamoxifen Citrate Loaded Sustained Microspheres

Biodegradable polymer carriers have been widely used as parenteral controlled release systems.The researches of anti-tumor drugs and antipsychotic drugs loaded microspheres have also made a considerable progress.Biocompatible and biodegradable Poly(lactic-co-glycolic acid)(PLGA)was chosen as carrier polymer and tamoxifen citrate(TMC)as model drug.The microspheres were prepared by simple emulsion(O/W)and solvent extraction method.The anti-tumor drug loaded microspheres were injected and acted as a"reservoir"in the local tissue to realize the sustained release of the drug in the body.As a result,the drug concentration was maintained at a high range in the tumor tissue for a long time,reducing the concentration of the drug in the normal organs and the fluctuation of in the blood.Therefore,it reduced the toxic and side effects compared with systemic chemotherapy,and improve the compliance of patients.Particle size,drug loading and entrapment efficiency of the microspheres were used as comprehensive evaluation indexes.PLGA concentration,PVA concentration and oil phase volume ratio of water phase were selected by single factor method.Central composite design and response surface methodology(CCD-RSM)were adopted to optimize the prescription with an average particle size of8.75±0.16?m,considerable encapsulation efficiency of 88.21±1.63%and drug loading of 9.30±0.16%.The results of scanning electron microscopy showed that the microspheres were uniform,round and without holes on the surface.The results of X-ray diffraction showed that the drug existed in the amorphous form in the microspheres.The in-vitro TMC released from microspheres in a bi-phasic release manner,characterized by a constant release in the initial phase with no burst release which fitted well with Zero order release dynamics(Q=2.7934+4.8865t,R~2=0.9963).The second release phase had a good fit with the First order release dynamics(ln(100-Q)=4.3134-0.05034t,R~2=0.9897).The diffusion,erosion of microspheres and osmotic pressure were inferred as the main release mechanisms.In the in-vivo pharmacodynamic test,the group of mice peritumorally subcutaneously injected with TMC loaded microspheres suspension had significant anti-tumor effect comparing with the groups of pure TMC suspension and isotonic saline.The tumor inhibition rates of experimental group and control group were 16.79% and 51.22% respectively.