Experimental Study And Physiological Modeling Of Nano-magnetic-insulin For Blood Glucose Control

People have made great efforts for the treatment of diabetes for many years.For patients with type 1 and advanced type 2 diabetes,it is always a huge challenge to achieve accurate insulin infusion and reasonable treatment.For insulin infusion control,a closed-loop system capable of autonomously controlling the amount of insulin injection based on blood glucose concentration has been a better choice.Although the dose of insulin release by the closed-loop system is determined by the system controller,the effect of insulin in the organism is often uncontrollable.In this study,in order to active control insulin effect in vivo,we coupled insulin molecules covalently onto Fe3O4 nanoparticles inspired by the researches of drug-delivery nanoparticles.The goal is to prepare the nano-magnetic-insulin(MNPs-Insulin)with hypoglycemic effect inherited from insulin and magnetic control ability to regulate its in vivo effect.In vitro and in vivo experiments and physiological modeling were applied to characterize and validate the properties of obtained nano-magnetic-insulin.The research content of this study mainly contains:(1)The structure,morphology and properties of MNPs-Insulin were analyzed by infrared characterization(FTIR),elemental analysis(EA),scanning electron microscope analysis(SEM),hydrated particle size analysis(DLS),and thermogravimetric analysis(TGA);(2)The blood glucose control ability and relating biocompatibility of MNPs-Insulin were validated through a series of experiments of peritoneal injection of MNPs-Insulin in diabetic mice and Prussian Blue and H&E staining of tissue sections;(3)The magnetic responsiveness of MNPs-insulin in the peritoneal area and the feedback adjustment of blood glucose concentration of MNPs-insulin with different particle sizes were analyzed and verified through external magnetic field attraction modeling in Comsol and physiological modeling of peritoneal glucose-insulin system in MATLAB.The results are shown below:(1)The material characterizations confirmed the successful combination of insulin and magnetic Fe3O4 nanoparticles;(2)The relating animal experiments confirmed the blood glucose regulation ability of MNPs-Insulin and also showed that MNPsInsulin has a longer effective drug duration.The biocompatibility analysis also showed good biocompatibility of MNPs-Insulin;(3)VSM results and Comsol simulation results showed good magnetic control of MNPs-Insulin.Glucose-Insulin model simulated the effect of MNPsInsulin injection of different sizes in Type 1 diabetic patients body,and the blood glucose concentration of nano-magnetic insulin with a larger particle size fluctuated more smoothly.