Studies On Preparation And Properties Of Biobased Glucose Responsive Carriers

Diabetes is harmful to human health and becoming more and more serious in the worldwide.The traditional treatment is parenteral injection.Although injecting insulin can help maintain the normoglycemia,major drawbacks are remained: the actual injected dosage of insulin does not match the actual need,resulting in hypoglycemia.If the amount of insulin administered can be adjusted dynamically according to the blood glucose concentration in time,this defect can be avoided.Therefore,based on the principle of glucose responsiveness,this paper develops three bio-based controlled release carriers,which throw important theoretical significance to the treatment of diabetes.In this paper,sugar-responsive gels or nanoparticles are prepared based on phenylboronic acid modified bio-based macromolecules.Responsive carriers were prepared by using different response principles of modified polysaccharides and peptides,and the stability,sugar responsiveness,and controlled release behaviors of insulin(Ins)were investigated to prepare a practical drug controlled release carrier.1.Preparation and properties of ?-polyglutamic acid-phenylboronic acid /cationic guar gum gelThe ?-polyglutamic acid-phenylboronic acid(?-PGA-PBA)were synthesized by conjugating 3-aminobenzeneboronic acid(APBA)to ?-polyglutamic acid(?-PGA).The guar gum(GG)was modified by 2,3-epoxypropyltrimethylammonium chloride(CHGTA)to endow with better water solubility.The gel with glucose responsiveness was prepared by mixing ?-PGA-PBA and cationic guar gum(CGG)in a certain ratio.Rheological test showed that the gel demostrated shearing thinning behavior,making it can be injected by a syringe;furthermore,the sugar responsiveness and drug controlled release behaviors were investigated.The results showed that the gel could dissociate in the 4 mg/mL glucose solution,and the loading insulin could be released faster in high glucose solution.2.Preparation and properties of ?-polylysine-phenylboronic acid/cationic guar gelIn order to prepare bio-based gel with better stability and sugar responsiveness,polyamino acid of lower molecular weight is used in this route.?-Polylysine-phenylboronic acid(?-PL-PBA)was synthesized by conjucating 4-formylbenzeneboronic acid(FPBA)to ?-polylysine(?-PL).Rheological test showed that the strength was negligible affected by the degree of modification of ?-PL but affected by weight percentage.Meanwhile,the gel demostrated shearing thinning behavior,so it can be injected by a syringe;Investigation of sugar responsiveness and drug release performance shows that the gel was disintegrated after imersing in a 4 mg/mL glucose solution.At a high concentration,insulin could be released faster from the gel.MTT test results showed that the gel had no cytotoxicity,high cell survival rate.3.Preparation and properties of ?-PL-PBA/Ins/GOx nanoparticlesIn order to obtain a faster responsive carrier,nanoparticles were prepared by co-assembly of ?-PL-PBA,Ins and glucose oxidase(GOx).The particle size of nanoparticles was measured by nanometer particle size analyzer.It was found that when the pH was less than 7,the particle size of micelles increased with the increase of pH value.Scanning electron microscopy(SEM)showed the micelles with a diameter of 100 nm and a spherical shape.The results of sugar responsiveness and drug release performance indicated that the micelles are stable in the absence of glucose and responsive in the presence of glucose.MTT test results show that ?-PL-PBA had no cytotoxicity,high cell survival rate and good cell morphology.In this study,three kinds of bio-based sugar responsive carriers were prepared through reasonable design.The data showed that the carrier has glucose responsiveness and biocompatibility,and it is expected to be applied to cell culture,drug controlled release and in other biomedical applications field.