Studies On Preparation And Hypoglycemic Effect Of Composite Microspheres With Halloysite Nanotubes Loaded Insulin

Objective:To prepare alginate(ALG)/lecithin(LCT)/halloysite nanotubes(HNTs)/insulin(INS)composite microspheres,and characterize their physicochemical,biocompatibility and hypoglycemic properties,further to explore a potential application in the treatment of diabetes.Methods:The HNTs/INS was prepared by vacuum.Fourier transform infrared(FTIR)and X-ray diffraction(XRD)were used to analyze the binding between INS and HNTs.Transmission electron microscope(TEM)was applied to investigate HNTs size distribution and structure of HNTS/INS.Then,the composite microspheres were prepared by high-voltage electrostatic method.Inversion fluorescence microscope and scanning electron microscope(SEM)were used to observe the particle size distribution and surface morphology of the microspheres,the swelling performance and release profiles were also evaluated at different values of pH in vitro.The bio-safety of the composite microspheres was tested by cytotoxicity test and acute oral toxicity test,and its hypoglycemic effect was evaluated by oral hypoglycemic experiments in diabetic rats induced by STZ.Results:SEM images demonstrated that HNTs have nanometer size.FTIR,XRD and SEM showed that the insulin existed in the lumen of HNTs and had no effect on the crystal structure of HNTs.The composite microspheres prepared by high-voltage electrostatics possessed a pH-responsiveness with uniforrm size,and its outer-surface was dense,but the inside loose,which benefited to insulin load.The change of the microsphere size in the simulated gastric juice(pH 1.2)was small,not exceed 20μm,but it was more sensitive in pH 7.4 and increases about 300μm after 2h.Meanwhile,it released INS with a First Order model which exhibited a certain sustained release performance.The cytotoxicity experiment and acute oral toxicity test indicated that the composite microspheres had a good biocompatibility.The Hypoglycemic experiments demonstrated that the composite microspheres had certain hypoglycemic activity.Conclusion:The intelligent pH response system for oral controlled-release delivery of insulin was a relatively safe and effective drug delivery system,and it had great potential to achieve insulin oral administration for the treatment of diabetes.