Preparation And Characterization Of Polygonatum Polysaccharide-Based Temperature Sensitive Material

Due to the high frequency of traditional drug delivery and poor compliance of patients,intelligent drug delivery systems have been widely studied,such as thermosensitive injectable materials — hydrogels.Thermosensitive hydrogels with various activities have not been reported.Polygonatum polysaccharides have many activities.If prepared into thermosensitive hydrogels,they may play a synergistic role in anti-cancer,hypoglycemia,immune regulation and so on,and reduce the amount of drug substances.However,there is no report on the preparation of thermosensitive materials from Polygonatum polysaccharide.In this paper,Polygonatum polysaccharide with certain biological activity was selected to explore the feasibility of preparing thermosensitive materials.Thermosensitive hydrogels with certain mechanical properties and sustained release were prepared,and thermosensitive copolymer micelles were synthesized by EDC cross-linking method,and their properties were evaluated.1.Extraction and Chemical Modification of Polygonatum sibiricum polysaccharideThe polysaccharide concentrate is extracted by the method of extracting alcohol by water.The polysaccharide is subjected to cationization,aldehyde grouping and amination modification using the reactive group hydroxyl group in the Polygonatum polysaccharide.According to qualitative analysis,three modified polysaccharides have been successfully prepared.The content of the groups in the three polysaccharides was measured.2.Preparation and Characterization of Temperature Sensitive Chitosan/Yongjing Polysaccharide-Montmorillonite HydrogelNatural bentonite was purified and modified by sodium.X-ray diffraction(XRD)showed that sodium montmorillonite(Na-MMT)had been successfully prepared.The properties of sodium modified montmorillonite were characterized by blue absorption,swelling value,swelling capacity,colloid value,etc.The purity of sodium modified montmorillonite was increased from 49.95% to 83.41%,and the cation exchange capacity was also increased to 90 mmol/g.Na-MMT was organically modified by using quaternary ammonium salt group in etherified polysaccharide prepared in Chapter 1.Organically modified montmorillonite with different interlayer spacing was prepared by changing the content of etherified polysaccharide.When the content of polysaccharide was doubled as cation exchange capacity(CEC),the maximum interlayer spacing was 2.15 nm.The drug loading analysis showed that the drug loading of organic modified montmorillonite could reach 720 mg/g.Thermosensitive hydrogels containing organically modified montmorillonite(PMMT)with different concentrations were prepared using chitosan as material,and their properties were evaluated.The experimental results show that some kinds of hydrogels have obvious pore structure.With the increase of PMMT content,the internal space of the gel first becomes larger,and the pore size becomes smaller due to the inclusion of montmorillonite particles.The swelling experiments show that the swelling rate of the hydrogel is the highest when the content of PMMT is 4%,whether in acidic,neutral or alkaline conditions.For the determination of the degradation rate of hydrogels,it can be found that when pH=2,the degradation rate of hydrogels decreases with the increase of MMT content;when pH=7.4 and pH=12,the degradation law is opposite.Rheological experiments show that the hydrogel prepared has a temperature sensitive property.The elastic modulus of the gel increases with the increase of temperature.When the content of PMMT is 4%,the elastic modulus reaches the maximum of 6789 Pa,and the pure chitosan hydrogel is only 1061 Pa.It is indicated that the addition of PMMT can effectively improve the mechanical strength of gels.When BSA was used as a macromolecular drug model to evaluate the in vitro release of hydrogels,it was found that the release rate of hydrogels with modified montmorillonite was the slowest,while that of pure chitosan hydrogels was the fastest,which may be attributed to the release mechanism of drugs in hydrogels.Cytotoxicity tests showed that the toxicity ratings of the prepared hydrogels were in grade 0 or 1,which met the requirements of drug delivery system.3.Preparation of Polygonatum sibiricum Polysaccharide /Poly-N-isopropylacrylamide CopolymerN-isopropylacrylamide(NIPA)is an amphiphilic polymer consisting of hydrophilic amide bond and hydrophobic isopropyl group.It can exhibit volume phase transition when the critical dissolution temperature is higher than its low critical dissolution temperature.In this chapter,Polygonatum sibiricum polysaccharide/PNIPAAm thermosensitive copolymer was synthesized.The polymer PNIPAAm-COOH with carboxyl end group was synthesized by free radical polymerization of monomer NIPA.The polymer was successfully synthesized by infrared,carbon spectrum analysis.The content of carboxyl group in polymer was titrated by acid-base titration,and the molecular weight of polymer was calculated.APSP/PNIPAAm copolymers with different grafting rates were prepared by EDC crosslinking.The low critical dissolution temperature of the copolymer was observed and its temperature sensitive behavior was analyzed by dynamic light scattering.The application and other characterization of the copolymers need to be further studied.