Preparation,Characterization,and Evaluation In Vivo Of Insulin-loaded Silica Nanosphere Coated With HP55 For Oral Delivery Of Insulin

Insulin is the most effective and durable drug in the treatment of advanced-stage diabetes.Pain associated with the injection and risk for infection at the injection site cannot be completely avoided,and a much simpler,non-invasive method has long been desired.However,oral delivering insulin was a tough task for rapid enzymatic degradation.In this work,we designed and developed a delivery system composed of enteric nanosphere for oral delivery of insulin.The silica was selected for loading insulin,which surface has a lot of pores with a powerful adsorption capacity,advantages for permeability and slow-release.The Ins-SiO2 obtained was coated with the hydroxypropyl methylcellulose phthalate(HP55)by desolvation method,which is a good enteric coating material.The Ins-SiO2-HP55 obtained was characterized by Transmission electron microscope(TEM),(BET),Fourier-transform infrared(FT-IR),Differential scanning calorimetry(DSC),thermogravimetric analysis(TGA)and X-ray diffraction(XRD).This Research derived that:1 The optimum insulin loading conditions were determined as follows:the pH of solution is 2.8,the adsorption time is 24 h,the adsorption temperature is 40 ? and the insulin concentration is 1.413 mg/mL.In these conditions,the drug loading of Ins-SiO2 is 9.27%.2 The Ins-SiO2-HP55,an enteric nanosprere of insulin obtained were characterized by Tra nsmission electron microscope(TEM),surface area,Fourier-transform infrared(FT-IR),X-ray diffraction(XRD),Differential scanning calorimetry(DSC)and Thermogravimetric analysis(TGA).The results showed that insulin was loaded most in the pores of silica,while the HP55 coated on the extent of Ins-SiO2.3 The results of adsorption model were suggested that the silica load insulin is mainly the result of the physical adsorption.The Langmuir and Freundlich equation can be a good description on their nano-silica adsorption process when the range of concentration of insulin is 0.17?1.413 mg/mL.The quasi-two rate equation can well describe the adsorption kinetics of nano-silica through the research of the model of adsorption kinetics.The quasi-two rate equation on nano silica to insulin is:t/q=1/0.2687+t/7.7284 The results of release in vitro showed that the release of insulin from Ins-SiO2-HP55 was markedly reduced in simulated gastric fluid(SGF).By contrast,the release amount of insulin from Ins-SiO2-HP55 was increased significantly in simulated intestinal fluid(SIF).5 In vivo evaluation on diabetic animals showed the blood glucose level of diabetic rats could be effectively reduced after oral administration Ins-SiO2-HP55.There is marked hypoglycemic effect after one hour of taking the Ins-SiO2-HP55.The time between 3 h to 7 h,the GLU of rats of the Ins-SiO2-HP55 stably kept from 4.85 mmol/L to 2.67 mmol/L that was significantly less than the normal level(6.7 mmol/L).However,the GLU of diabetic rats which oral administration the pure insulin stably kept from 8.03 mmol/L to 6.56 mmol/L that was significantly more than the normal level(6.7 mmol/L).These results suggested that Ins-SiO2-HP55 could have potential value in oral administration systems of diabetes chemotherapy.