| Ugi reaction is one of the most famous multi-component reactions.Ugi reaction refers to the process of using ketones or aldehydes,amines,acids and isocyanides as raw materials to form amide compounds with H2O by-product.Ugi reaction has the advantages of simple operation,mild conditions,high yield,high efficiency,molecular diversity,and atomic economy.These advantages make the reaction green,and produce materials that are biocompatible and environmentally friendly.Based on this,Ugi reaction has been used widely in many fields.In this study,Ugi reaction was used to successfully prepare antibacterial materials and drug carriers with good biocompatibility.The main contents and conclusions are as follows:1.Synthesis,characterization and biological properties of fluorescent labeled piperazine antibacterial polymer:（1）Using 4-bis-（3-aminopropyl）piperazine,7-N,N-diethylamino-3-aldehyde coumarin,800-ethyene glycol disuccinate（S-PEG-800）,tert-butyl isonitrile,benzaldehyde as raw materials,A novel piperazine-based fluorescently labeled antibacterial polymer PC was prepared by Ugi reaction.The PC was characterized by Nuclear magnetic resonance spectrometer（NMR）,Fourier transform infrared spectrometer（FTIR）and Gel permeation chromatography（GPC）,the results showed that polymer PC were successfully synthesized.（2）The filter paper method and bacterial growth curve method were used to investigate the antibacterial performance of PC.The results showed that the concentration of 50 mg/ml PC against Escherichia coli（E.coli）and Staphylococcus aureus（S.aureus）has a significant inhibitory effect,and the inhibitory effect on E.coli is more obvious.（3）The cytotoxicity of PC was evaluated by MTT and AM-PI double staining method.The results showed that PC at a concentration of 100μg/ml did not produce significant cytotoxicity after incubating the cells for 72 h.（4）Live cell imaging studies indicate that PC easily enters the cell and emits light,and the fluorescence intensity gradually increases as the concentration increases;24 h long-term imaging and fluorescence stability experiments show that PC has good fluorescence stability;The photobleaching recovery experiment shows that PC has good molecular fluidity.Therefore,polymer PC can be used as a biological material that has both fluorescent labeling ability and antibacterial properties,and is harmless to the human body.2.Preparation of sodium alginate gel by Ugi reaction and its drug release in vitro:（1）Using sodium alginate（NaAlg）,ethanolamine,and t-butylisocyanide as raw materials,and glutaraldehyde at different concentrations as cross-linking agents,poly（sodium alginate/glutaraldehyde/ethanolamine/t-butylisocyanide）Gel-NaAlg-Ugi and NaAlg-Passerini were synthesized through multi-component reaction of Ugi and Passerini,to modify the sodium alginate.（2）The products were characterized by FTIR and scanning electron microscope（SEM）,and some products were selected for X-ray diffraction analysis（XRD）,equilibrium swelling rate test,Thermogravimetric analysis（TGA）,specific surface analysis and rheological performance analysis.The results show that NaAlg-Ugi and NaAlg-Passerini are successfully synthesized;NaAlg-Ugi has a porous network structure,while NaAlg-Passerini has a rough and collapsed morphology,and the pores are not obvious and uneven.The swelling rate of NaAlg-Ugi（450%）is higher than that of NaAlg-Passerini（200%）;The thermal decomposition temperature of NaAlg-Ugi and NaAlg-Passerini is about 250℃;NaAlg-Ugi exhibits gel-like viscoelastic behavior.（3）Adsorption of doxorubicin（DOX）using NaAlg-Ugi as a carrier,and studying its drug loading performance and drug release performance under different ratios of glutaraldehyde crosslinking（10%,20%,50%,80%）,The results show that the higher the glutaraldehyde content,the higher the drug loading,the lower the cumulative release,and the release equilibrium is reached in a shorter time.10%-NaAlg-Ugi as the object of the release study at different pH,found that the release of NaAlg-Ugi-DOX has pH sensitivity,when pH=3,the cumulative release amount is as high as 97%,while pH=5.4 The cumulative release is relatively low at 58.14%.（4）In addition,the cytotoxicity of NaAlg-Ugi/NaAlg-Ugi-DOX/DOX in different cell lines was studied by live cell imaging and MTT.The results showed that NaAlg-Ugi is non-cytotoxic.While NaAlg-Ugi-DOX and DOX have obvious inhibitory effects on MCF-7 cells,Hela cells,A549 cells,and HepG2 cells,with increasing concentration and time,the inhibitory effect is more obvious.And the cytotoxicity of NaAlg-Ugi-DOX is lower than that of DOX at the same concentration,but when the time is as long as 72 h and at a higher concentration,the cytotoxicity of NaAlg-Ugi-DOX and DOX are basically the same,which indirectly proves that Slow-release behavior of NaAlg-Ugi-DOX.Therefore,this type of hydrogel has excellent biocompatibility and drug release properties,and is expected to become a carrier for targeted drug release,and has good application prospects in biomedicine. |
