Study Of Sustained-release Insulin/PLGA Microspheres

At present, insulin is one of the most effective drugs for the treatment of diabetes, butthere are some limitations by using oral administration. Insulin is unstable, and has alower bioavailability by oral administration due to the acidic environment of stomachand the degradation of enzymatic. Subcutaneous injection of insulin is commonly used asthe treatment method for diabetic patients. Long-term frequent injections take a greatdeal of pain, such as the tissue lesions at the injection site, symptoms of hypoglycemia, etal, which reduce the compliance of patients. Therefore, developing a new deliverysystem is very important. In numerous studies, long-term sustained release microsphereformulations, can protect the stability of insulin, decrease the number of subcutaneousinjection, and improve the compliance of patients.In this study, INS/PLGA microspheres were prepared via solvent evaporationtechnique. The experiments investigated the preparation factors of microspheres,including the concentration of PLGA, different drug-loading and the concentration ofPVA, compared the different preparation methods (W/O/W and S/O/W). The mostappropriate preparation conditions were determined. The characteristics of the resultantmicrospheres were detected by scanning electron microscope (SEM), infraredspectroscopy (FT-IR), differential scanning calorimetry (DSC). The drug-loading andencapsulation efficiency of microspheres were also measured. The study found that theresultant microspheres were smmoth, particle size distribution was between50and150μm, entrapsulation efficiency of medicated microspheres was74.01%. The analysis ofFTIR and DSC indicated INS was entrapped into microspheres.During the experiments of vitro release of microspheres, the influence of theconcentration of PLGA, different drug-loading and the concentration of PVA to therelease behavior were analyzed, and at the same time, the vitro release and thedegradation of polymer for different drugs medicated microspheres were compared. Thestudy showed that the release rate of the microspheres affected by the physic-chemicalcharacters of drugs, within a period of time, the drug vitro release rate was faster, if thedrug solubility in the release medium was larger. The cumulative release percent of INSmicrospheres was89.3%at30d.In the animal experiment, male Wistar rats were used as the model animals. Themodel diabetes rats were established via intraperitoneal injection of alloxan. The study explored the effects on hypoglycemic of subcutaneous injected the insulin microspheres.The results indicated that the insulin in PLGA microspheres still maintained its activity.The relative biood glucose of diabetes rats was reduced from100%to40%, there was acertain effect of antidiabetics. Simultaneously, the insulin concentration of model ratswas measured by Insulin Elisa Kit at different time intervals, the range of insulinconcentration in vivo was between4mIU and8mIU. What’s more, the Pearsoncorrelation studies showed that the in vivo release of INS/PLGA microspheres wasrelated to the in vitro release of microspheres, the correlation coefficient (R) was0.9237.