Preparation And Performance Characterization Of PH/redox Dual Response Dextran Hydrogel

The pH/redox dual responsive hydrogel as a kind of smart hydrogel can respond to environmental stimuli.Its chemical structure can be changed according to changes in pH and redox conditions.What's more,as drug carriers,the environmental sensitivity release of drugs can be achieved as drug carrier.Dextran has good water solubility,biodegradability and biocompatibility as a natural polymer.Therefore,in this paper,dextran is used as the basic material,and cysteamine dihydrochloride(CYS)is used as a crosslinking agent to prepare hydrogel.Preparation of dextran nanogel containing Schiff base and disulfide group in this structure was by reverse microemulsion method.The nanogel were used as drug carriers to carry the anticancer drug(DOX·HCl),and their pH/redox-responsive degradation and drug release behavior were studied.The main research contents are as follows:1.The aldylated dextran solution was prepared by sodium periodate oxidation method,and aldehyde-based dextran was used as a basic substance,CYS was used as a crosslinking agent.Hydrogel was prepared with using an aldehyde group to amino group molar ratio of 1.485.The nanogel was prepared by the method of reverse microemulsion to prepare the nanogel with dextran which molecular weight of 40000.The prepared nanogel had good spherical morphology,and the surface of the nanogel was smooth and well dispersed.The average particle diameter of the nanogel was409.03 ± 70.76 nm.2.The hydrogel has pH/redox dual responsive due to the Schiff base and the disulfide bond group in its structure.It can be degraded by hydrolysis of Schiff base or cleavage of disulfide bond under acidic or reducing conditions.The degradation behavior of hydrogel and nanogel under different pH values(5.0;6.5;7.4),different concentration GSH solution(10 mM?5 mM?10 ?M)and synergistic effect of pH/GSH was studied.Rheological experiment results show that the storage modulus(G')decreases as the pH of the environment decreases and the concentration of GSH increases and the hydrogel has a lowest storage modulus(G')value in a synergistic environment.SEM results show that in the low pH and high concentration GSH degradation solution,the hydrogel network structure will undergo hydrolytic cleavage,resulting in collapse and fusion of the microscopic pores.The degradation behavior ismost significant under the synergistic effect.The microstructure of the hydrogel did not change significantly in solution with pH of 7.4 and GSH solution at concentration of 10 ?M and all of them had a relatively uniform macroporous structure.During the degradation of hydrogel microspheres,as the pH value of the buffer decreases and the concentration of GSH increases,the hydrogel network structure undergoes hydrolytic rupture,resulting in a loose three-dimensional network structure inside the microsphere.The hydrogel microspheres are expanded in volume,thereby destroying the spherical morphology of the microspheres.The degradation behavior that occurs under synergy is most pronounced.The micro-spherical appearance did not change significantly in solution with pH of 7.4 and GSH solution at concentration of 10 ?M.The above results indicate that the degradation behavior of the dextran hydrogel has both pH and redox responsiveness.3.The anticancer drug DOX·HCl was used as the drug model,and the nanogel were used as drug carrier to study drug loading and pH/redox sensitivity release behavior.The nanogel can be used to payload DOX by covalent bonding of Schiff bases.The drug loading capacity was 3.1527% and the drug loading efficiency was35.4675% which were calculated by ultraviolet spectrophotometer.DLS and SEM results showed that the drug-loaded nanogel had a larger particle size than that before drug loading,and the average particle size in the aqueous solution was 739.12 ±129.16 nm.The in vitro drug release behavior study showed that the drug release behavior of DOX @ Dex nanogel had pH/redox dual responsive.As the pH of the buffer decreases and the concentration of GSH increases,the rate of drug release increases,and the cumulative drug release increases.Under the synergistic effect of pH/redox,the drug release rate is the fastest,and the cumulative release content within160 h is as high as 88.38%.What's more,the release curves under three environmental conditions have the characteristics of initial burst release and slow release later.4.The toxicity of drug-loaded nanogel in different cancer cells in vitro was investigated by CCK-8 method.It was verified that the constructed drug carrier has good biocompatibility to cells.The survival rate of cancer cells has a strong dependence on drug concentration and culture cycle,the higher the drug concentration,the longer the culture cycle,and the lower the cell survival rate.Cell labeled experiments were performed on cancer cells which treated with drug-loaded nanogel and doxorubicin hydrochloride using a laser confocal scanning microscope.The resultsof confocal characterization showed that the drug-loaded nanogel and doxorubicin hydrochloride were similarly effective in labeling cancer cells.