Study On Injectable Hydrogel Drug Delivery System Based On Dextran And Zwitterion Groups

Hydrogel is a soft material with a three-dimensional network structure,high water content and high flexibility.The injectable drug-loaded hydrogel can be directly injected into the lesion site to form a drug reservoir in the original position,which can significantly improve the therapeutic effect and reduce the damage to normal human tissues.In this study,an injectable hydrogel was prepared based on dextran and zwitterion groups,and its application was studied in a mouse melanoma model.Using the hydrogel to deliver drugs can prolong the time of action at the tumor site and improve the therapeutic effect.Here,two precursors containing double bonds and sulfhydryl groups were first prepared,which can form an injectable hydrogel with good biocompatibility through "click chemistry"reaction.The chemotherapeutic drug doxorubicin(DOX)and the indoleamine 2,3-dioxygenase(IDO)inhibitor 1-methyl-tryptophan(1MT)were loaded into the dendrimer polyamidoamine(PAMAM).And the outer layer was coated with macrophage membrane to prepare PDOX/1MT@MM.Then,the P-DOX/1MT@MM was loaded into the hydrogel to study its effect as a drug carrier.The specific research contents are as follows:(1)Synthesize precursors and hydrogels,and characterize them by NMR,infrared,etc.The rheological experiments and swelling experiments showed that the properties of the hydrogels could be adjusted by different precursor concentrations.The cytotoxicity experiments confirmed the good biocompatibility of the hydrogels.The anti-protein experiment proved that the hydrogel has the characteristics of anti-protein adsorption.The degradation experiments showed that the hydrogels would gradually degrade in vivo.(2)The P-DOX/1MT@MM was prepared by encapsulating DOX and 1MT with PAMAM as a carrier,and coated with macrophage membrane.Then it was characterized by particle size,potential and transmission electron microscopy.The cytotoxicity experiments showed that it had strong cell killing ability at higher DOX concentrations.(3)The drug-loaded hydrogel was prepared by mixing the preparation and the precursors,and its properties were investigated by experiments.The release curve indicated that the drugloaded hydrogel could have a sustained release effect on the drug.The cytotoxicity experiments demonstrated that the drug-loaded hydrogels could release drugs to kill tumor cells.The cell uptake experiments,apoptosis experiments and cell immunogenic death experiments showed that the hydrogel had sustained drug release,and P-DOX/1MT@MM had better effect than PDOX/1MT.(4)The therapeutic effect of the drug-loaded hydrogel on B16F10 melanoma mice was further studied.The results of in vivo imaging experiments of small animals showed that the hydrogel could stay in the tumor site for a long time.The results of postoperative antirecurrence,distant tumor experiments and lung metastasis experiments showed that the therapeutic effect of the drug-loaded hydrogel group was better than that of the solution group,and it had good safety in vivo The analysis of lymphocytes in vivo showed that the drug-loaded hydrogel could induce an immune response to achieve therapeutic effect.In conclusion,the use of this hydrogel for drug delivery is a very promising therapeutic modality.