Study On HA-GMS-INS Insulin Oral Nano Drug Delivery System

Objective:Glyceryl monostearate(GMS)is combined with hyaluronic acid(HA)to synthesize the amphiphilic compound HA-GMS by esterification,thereby increasing the hydrophobicity of HA.Using HA-GMS as a carrier to prepare insulin(INS)water-in-oil(W/O)nanoemulsions to increase the stability of INS in the gastrointestinal tract and improve its oral bioavailability.Methods:The GMS-modified amphipathic HA vector HA-GMS was synthesized by esterification reaction.The degree of substitution was used as the evaluation index for the formulation screening,and the preparation process was optimized.The HA-GMS was characterized by infrared spectroscopy and nuclear magnetic resonance spectroscopy;the low energy emulsification method was used.To prepare blank nanoemulsion,and to investigate the effect of the concentration of prepared carrier HA-GMS on blank nanoemulsion;preparation of HA-GMS INS nanoemulsion HA-GMS-INS,the physical and chemical properties of HA-GMS-INS,in the gastrointestinal tract The in vitro cumulative release and anti-enzymatic activity of the solution were investigated,and the hypoglycemic effect of HA-GMS-INS was further investigated in a mouse model of diabetes.Results:The optimal preparation process of HA-GMS is:the ratio of HA to GMS is 1:3,the optimal reaction temperature is 45℃,the rotation speed is 600 rpm,and the reaction time is 48 h.The average particle size of HA-GMS-INS is 37.19 nm.The appearance is a complete spherical shape with uniform size.In the simulated release medium of simulated gastric juice,the cumulative release of HA-GMS-INS reached about 40%at 2 h,and the drug substance was completely released at 10 min.The results showed that HA-GMS was used as the carrier for HA-GMS.-INS has a protective effect on insulin.In the simulated release medium of artificial intestinal fluid,the cumulative release of the HA-GMS-INS oral nano-drug delivery system was completely released at 6 h,and the INS raw material was released immediately after it was released into the release medium.In the enzymatic degradation experiment,HA-GMS-INS oral nano-drug delivery system has a protective effect on INS both in artificial gastric juice and artificial intestinal fluid.Hypoglycemic experiments showed that:HA-GMS-INS oral nano-administration system has a certain degree of hypoglycemic effect,and raw drug group,blank control group did not show the effect of hypoglycemic.Conclusions:HA-GMS was successfully synthesized and HA-GMS-INS was prepared by low energy emulsification method.Moreover,the drug delivery system can improve the stability of INS in the gastrointestinal tract,and it can improve the oral hypoglycemic effect compared with the API.