Preparation Of A Nir-responsive Hydrogel And Its Application In Controlled Drug Release

Near-infrared(NIR)light-responsive hydrogels are the most promising local anticancer drug delivery system for cancer treatment.However,most currently reported NIR-light-responsive hydrogels were prepared by mixing thermosensitive polymers and photothermal conversion agents,most of which are thermo-degradable hydrogels.Due to the great influence of temperature,such hydrogels still have some problems in drug delivery and self-degradation in vivo.As a kind of important biological macromolecules,carbohydrates participate in many life processes,and their application in biomedical have been the focus of life science.In recent years,research on the development of carbohydrate drugs,preparation of novel saccharides,the relationship between structure and function of sugar compounds,and the interaction between sugars and other substances become more concentrated,the application of these in degradable hydrogel is particularly wide.In order to develop a new type of photodegradable hydrogel,we use a fructose polymer and a polymer grafted with phenylboronic acid half ester(BOB-HA)to form hydrogel(Gel-Fru-BOB),which was formed based on the interaction of dynamic covalent bond between fructose and phenylboronic acid in a neutral or alkaline environment.Because the segments of boron in dynamic covalent bond was peroxide oxidation off easily,so the photosensitizer and reductant ascorbic acid are added into the Gel-Fru-BOB,both in a certain wavelengths of light can produce hydrogen peroxide,which breaks the network structure formed by the two polymers to degrade the hydrogel,thus a light responsive hydrogel(Gel-PDS-Vc)produced.This paper mainly studies the following two aspects:(1)the effect of sugar isomeric effect on the binding ability of sugar to benzene borate hemiester structure: first,we synthesized two sugar polymers with different molecular configurations with similar molecular weight and molecular weight distribution,Poly(3-O-maipfru)and Poly(1-O-maipfru).In dilute solution,sugar polymer can self-assemble with BOB-HA to form nanoparticles,and the particle hydrodynamic radius and scattering light intensity analysis detected by dynamic light scattering(DLS)show that the binding ability of Poly(3-O-maipfru)and BOB-HA was stronger than Poly(1-O-maipfru).Hydrogels can be prepared in concentrated solution by controlling solid content and two-component ratio.The rheological property index detected in Bohlin rotatory rheometer indicates that the modulus and viscosity of the gel formed by Poly(3-O-maipfru)and BOB-HA are higher than that of Poly(1-O-maipfru),which also reflects that Poly(3-O-maipfru)has higher binding capacity with phenylborate semi-ester group from the macroscopic performance.In addition,it was also found in the experiment that two kinds of polymers could form gels in a wide range of mass ratios.On the premise of a total solid content of 10 wt%,the higher content of the sugar polymer lead the higher gel modulus and viscosity.In several ratios of the experiment,the highest modulus and viscosity were found when the mass ratio of the sugar polymer and the BOB-HA was 4:1.In addition,the high graft rate of BOB-HA is also beneficial to improve the mechanical properties of the hydrogel.(2)Application of Gel-PDS-Vc as a local anticancer drug delivery system in anticancer: the cytotoxicity and physiological toxicity of the hydrogel Gel-Fru-BOB in vitro indicates that the hydrogel has low biotoxicity,after carrying the photosensitizer and ascorbic acid,it will completely degrade within 10 min under the illumination of near-infrared light,so The small molecule anticancer drug doxorubicin(DOX)was then loaded into Gel-PDS-Vc for further in vivo and in vitro controlled drug delivery studies.In vitro drug release experiments showed that the drug release amount of Gel/DOX could reach 80% after one-time illumination,and the drug release rate could be effectively controlled by opening and closing illumination.In vivo degradation experiments showed that the hydrogel Gel-PDS-Vc can control the release of the drug by its own degradation;in the peritumoral experiment,the near-infrared window imaging system detected that DOX reached the highest enrichment on the tumor on the third day of gel injection.Gel/DOX effectively inhibits 4T1 tumors in anticancer therapy of 4T1 tumor-bearing mice.These results demonstrate that Gel/DOX has great potential for application in topical anticancer drug delivery.