Preparation And Properties Of Dynamic Bond Crosslinked Natural Polymer Based Drug-loaded Hydrogels

Hydrogel is a polymer with a three-dimensional cross-linked network structure,which has good biocompatibility and high water content.Drug delivery system(DDS)technology as a new system,it may be regulat in vivo drug distribution.The hydrogel due to its good biocompatibility DDS become a hot research.Vancomycin is an important antibiotic widely used in clinical medicine,and plays an irreplaceable role in some serious infections.In this dissertation,hydrazone cross-linking and Schiff base reaction are selected as cross-linking methods,and a vancomycin hydrogel drug-carrying system that can be used for injection is designed,and its in vitro release,antibacterial activity,cytotoxicity are evaluated.The main research contents of this paper are as follows:(1)Characterization of dynamically crosslinking injectable hydrogel: The precursors of adipic hydrazide(ADH)grafted polyglutamic acid(PGAADH)and oxidized dextran(OD)were synthesized.Without adding any additives,PGAADH is mixed with OD buffer solution to form a hydrogel through a dynamic covalent hydrazone bond.Hydrogel gel time between 15 s to 1min.Scanning electron microscope(SEM)image shows that the hydrogel with good pore structure are interconnected pore size in the 10-100 mm,highly porous structure is conducive to encapsulated cells and other biomedical applications.PGAADH/OD(PD)hydrogels have sufficient mechanical strength,between 4.01-10.42 k Pa.Rheological test showed the storage modulus ratio of the precursor can be controlled by varying the hydrogel.Swelling ratio of the hydrogel during degradation increases,24 h after reaching 28.9,showed a total holding capacity of the hydrogel can be maintained over a long state.(2)Evaluation of dynamic cross-linked hydrogels: In vitro drug release experiments show that vancomycin is released from PD hydrogels in a slow and continuous manner,and the amount of drug release decreases with the decrease of the PGAADH precursor content in the hydrogels.The cumulative release percentage of PD31 hydrogel in 5 days reached 34.87%,showing a good sustained release effect.ITC experiments demonstrated the hydrogel PD factors affect the drug release rate is mainly the interaction between the drug and the precursor molecule.In the antibacterial experiment,all the bacteria treated by the vancomycin hydrogel drug-carrying system shrank or ruptured,indicating that vancomycin still maintains good drug activity.The MTT experiment showed that the cell viability value of the hydrogel group exceeded 100%,which proved that the PD hydrogel has good biocompatibility.Encapsulation and culture experiments of He La cells in PD11 hydrogels showed a significant increase in cell population density,indicating that He La cells can proliferate in the 3D microenvironment of hydrogels,and proving that PD hydrogels have the ability to effectively act as extracellular matrix mimics.(3)Characterization of Gelatin/Oxidized Salecan injectable hydrogel: Synthesized the oxidized Salecan(OS)precursor.Through the Schiff base reaction,without adding any additives,the gelatin buffer is mixed with the oxidized salecan buffer to form a Gelatin/Oxidize Salecan(GS)hydrogel.GS41 hydrogel has the fastest gel time under physiological conditions of PBS 7.4,about 60 s.SEM was used to characterize the microstructure and morphology of the lyophilized GS41 hydrogel.The results showed that the hydrogel has a good through-pore structure with a pore size of 10-100 μm.The compressive strength of GS hydrogel gradually decreases with the increase of OS content,and the compressive strength of GS41 is the highest,which is 80.77 KPa.The realization of rheology indicates that the hydrogel has adjustable mechanical strength.In vitro enzyme degradation and swelling experiments confirmed the biodegradability and good water retention of the hydrogel.(4)Evaluation of gelatin/salecan hydrogel: Drug release experiments showed sustained release of vancomycin from the PD hydrogel,five days later,to 32.01%,showing good sustained release behavior.The morphology of the bacteria before and after the culture was observed with SEM.The bacteria shrunk or ruptured after treatment with the vancomycin hydrogel drug-carrying system.The GS hydrogel has a good encapsulation and protection effect on the drug.GS hydrogel co-cultured He La cells,the results showed no significant difference in cytotoxicity between all groups GS hydrogel.He La cells can proliferate in the 3D microenvironment of the hydrogel,indicating that GS11 hydrogel is a promising 3D cell culture substrate.