Glucose-sensitive Nanogels: Preparation And Application In Regulating Blood Glucose

Background and Objective:Diabetic Mellitus(DM)is a kind of metabolic disease with high blood glucose,which could lead to lots of chronic complications of nerve,blood vessels and other organizations.It is a serious threat to human health.With the improvement of people's living and the changes of lifestyle,the prevalence of diabetes increases year by year.Diabetic Mellitus has been the third killer of human health following cardiovascular disease and cancer,which brings a heavy burden to the society and the family.At present,the most direct and effective way to treat diabetes is to supply exogenous insulin.Although subcutaneous injections of insulin can quickly lower blood glucose,frequent times of injection will bring patients great physical and mental pain,which leads to poor tolerance and compliance of the patients.Therefore,it is of great practical significance to develop a kind of glucose-responsive system applied for self-release of insulin.The glucose-sensitive drug delivery system which is called "artificial pancreas" can simulate the physiological model of insulin secretion in the human pancreas,which controls the release of insulin and regulates blood glucose levels.Phenylboronic acid(PBA)could specifically bind to diols,which makes PBA and its derivatives have a good glucose-sensitivity.In recent years PBA-based glucose-sensitive polymer materials have attracted many attentions.This is a fully synthetic system with stable and long-term storage.It could be used for the self-regulation of drug release and have the advantage of reversible glucose response,which can be used as a carrier for regulating insulin release.At present,most PBA-based glucose-sensitive drug delivery systems are glucose-sensitive only in alkaline and high glucose concentrations(much larger than diabetic patients with blood glucose levels of 2.0 mg m L-1),and the materials used are not degradable,which limits its clinical treatment.In this study,a series of glucose-sensitive nano-gels were prepared by combining the phenylboronic acid with a biocompatible and biodegradable polyamino acid.It was used to carry insulin(INS)at physiologica L p H.In patients with diabetes,blood glucose levels quickly release a large number of drugs,and in the norma L range of blood glucose less release of drugs,with intelligent "open-off" type release characteristics.Methods:1)PGP was synthesized by using aminobenzeneboronic acid(APBA)and biocompatible poly(L-glutamic acid)-b-polyethylene glycol(PGA-b-PEG)as raw materials.Their structures were characterized by proton nuclear magnetic resonance(1H NMR)and Fourier transform infrared(FT-IR).2)The nanoparticles were prepared by self-assembly technique.Their morphology and particle size were characterized by transmission electron microscopy(TEM)and Dynamic light scattering(DLS).And insulin as the drug mode L,the determination of insulin drug loading and encapsulation efficiency and insulin in vitro release behavior.3)Using He La cell as a model,using Sodium dodecyl sulfate(SDS)as the positive control,the Methyl thiazolyl tetrazolium(MTT)method was used to test and evaluate the biocompatibility of sugar sensitive materials in vitro.Result:1)The synthesize of PGP was confirmed by 1H NMR and FT-IR,which was proved that this method could be used to synthesize PBA-based glucose-sensitive material,its structure is stable and accurate.2)The self-assembly of PGP was used to form glucose-sensitive nano-gel.The morphology and properties of PGP were characterized by CMC,TEM and DLS.The results showed that the particle size was uniform with the concentration of glucose And showed that PGP had certain glucose sensitivity at physiological p H.3)In vitro release studies have shown that nano-gel containing insulin in vitro release in two-phase mode,namely,rapid release stage and slow release stage.The release of insulin is mainly dependent on the change in the concentration of glucose around it.The release rate of insulin contained in PGP can be increased as the concentration of glucose in the surrounding environment increases.4)MTT method to detect the biological activity of PGP,from the cellular level proved PGP biocompatibility is good,is expected to become a glucose-sensitive nano-drug carrier.Conclusion:PGP has a response to the surrounding glucose concentration,while a good biocompatibility,structural stability is not easy to dissociate.Therefore,PGP is expected to be used as a biomedical protein for intelligent controlled release insulin to construct a bio-artificial pancreas.