An acid-sensitive delivery system based on acylhydrazone bond was developed for high loading and efficient delivery of doxorubicin.Doxorubicin(DOX)was covalently combined with dihydrazide adipate to form acid-sensitiv...An acid-sensitive delivery system based on acylhydrazone bond was developed for high loading and efficient delivery of doxorubicin.Doxorubicin(DOX)was covalently combined with dihydrazide adipate to form acid-sensitive hydrazone bond based on Schiff base reaction,then the intermediate was covalently combined with carboxymethyl chitosan through amide bond to form polymeric prodrugs,and nanoparticles were formed through self-assembling.Moreover,the structural and particle properties of CMCS-ADH-DOX were characterized by ultraviolet visible near infrared spectrophotometry(UV),nuclear magnetic resonance spectroscopy(^(1)H-NMR),fourier transform infrared spectroscopy(FT-IR),dynamic light scattering(DLS),and transmission electron microscopy(TEM).The mean diameter of the self-assembled nanoparticles is 165 nm,while the morphology is a relatively uniform spherical shape.Moreover,these DOXloaded nanoparticles showed pH-triggered drug release behavior.Compared with free DOX,CAD NPs showed lower toxic side effects in L929 cells and similar toxicity in 4T1 cells.The experimental results indicate that the CMCS-ADH-DOX nanoparticles may be used as an acid-sensitive targeted delivery system with good application prospect for cancer.展开更多
To synthesize three different grafting ratios of gallic acid(GA)-chitosan(CS)copolymer by a free radical mediated grafting method,which is further applied to the field of antibacterial materials,crosslinking structure...To synthesize three different grafting ratios of gallic acid(GA)-chitosan(CS)copolymer by a free radical mediated grafting method,which is further applied to the field of antibacterial materials,crosslinking structures of the compound GA-CS copolymer were characterized,fully indicating that gallic acid is resoundingly grafted onto chitosan.The grafting ratios of three copolymers GA-CS are 45.71%(Ⅰ),36.12%(Ⅱ),and 18.96%(Ⅲ)were determined by UV-Vis spectrophotometer.The minimum inhibitory concentrations of three GA-CS copolymers are 30μg/mL against Escherichia coli and are ranged from 250 to 550μg/mL against Staphylococcus aureus.By counting viable bacterial colonies,it can be found that antibacterial property is preferable by increasing the grafting ratio of GA-CS copolymers.Findings of investigation on aforementioned bacteria experiment indicate that the CFU/mL values of GA-CS(Ⅰ,Ⅱ,Ⅲ)are 2.04×10^(6),7.56×10^(6),1.48×10^(7) to Staphylococcus aureus,and 2.96×10^(6),1.01×10^(7),2.14×10^(7) to Escherichia coli after 12 h treatment.In addition,the interaction process between GA-CS copolymer and bacteria can be observed through a transmission electron microscope.The specific manifestation is that the bacterial cell membranes are ruptured after being treated with the copolymer,which causes the cell contents to flow out,and the cell morphology is shrunk and out ofshape.展开更多
A dual-receptor targeting delivery system based on acid-cleavage hydrazone bond was developed in the study. The characters of CMCS-hyd-CUR-EGFR-mAb were identified. The in vitro release studies revealed that this drug...A dual-receptor targeting delivery system based on acid-cleavage hydrazone bond was developed in the study. The characters of CMCS-hyd-CUR-EGFR-mAb were identified. The in vitro release studies revealed that this drug delivery system was acid-sensitive, and the self-assembled nanoparticles which were spherical. The in vitro results indicated that the dual-receptor targeting nanoparticles could be faster internalized into the Cal-27 cells via receptor-mediated endocytosis, which exhibited better antitumor activity than the one-receptor nanoparticles. The experimental results clearly reveal that CMCS-hyd-CUR-EGFR mAb provides a novel way for drug delivery in oral cancer treatment.展开更多
基金Funded by the Industrial Technology Research Institute of Hubei Provincial Department of Science and Technology(No.2020DEB012)the Hubei Provincial Department of Science and Technology Support Enterprise Technology Innovation Development Project(No.2021BAB119)。
文摘An acid-sensitive delivery system based on acylhydrazone bond was developed for high loading and efficient delivery of doxorubicin.Doxorubicin(DOX)was covalently combined with dihydrazide adipate to form acid-sensitive hydrazone bond based on Schiff base reaction,then the intermediate was covalently combined with carboxymethyl chitosan through amide bond to form polymeric prodrugs,and nanoparticles were formed through self-assembling.Moreover,the structural and particle properties of CMCS-ADH-DOX were characterized by ultraviolet visible near infrared spectrophotometry(UV),nuclear magnetic resonance spectroscopy(^(1)H-NMR),fourier transform infrared spectroscopy(FT-IR),dynamic light scattering(DLS),and transmission electron microscopy(TEM).The mean diameter of the self-assembled nanoparticles is 165 nm,while the morphology is a relatively uniform spherical shape.Moreover,these DOXloaded nanoparticles showed pH-triggered drug release behavior.Compared with free DOX,CAD NPs showed lower toxic side effects in L929 cells and similar toxicity in 4T1 cells.The experimental results indicate that the CMCS-ADH-DOX nanoparticles may be used as an acid-sensitive targeted delivery system with good application prospect for cancer.
基金Funded by the Health Commission of Hubei Province Scientific Research Project(No.WJ2019H275)。
文摘To synthesize three different grafting ratios of gallic acid(GA)-chitosan(CS)copolymer by a free radical mediated grafting method,which is further applied to the field of antibacterial materials,crosslinking structures of the compound GA-CS copolymer were characterized,fully indicating that gallic acid is resoundingly grafted onto chitosan.The grafting ratios of three copolymers GA-CS are 45.71%(Ⅰ),36.12%(Ⅱ),and 18.96%(Ⅲ)were determined by UV-Vis spectrophotometer.The minimum inhibitory concentrations of three GA-CS copolymers are 30μg/mL against Escherichia coli and are ranged from 250 to 550μg/mL against Staphylococcus aureus.By counting viable bacterial colonies,it can be found that antibacterial property is preferable by increasing the grafting ratio of GA-CS copolymers.Findings of investigation on aforementioned bacteria experiment indicate that the CFU/mL values of GA-CS(Ⅰ,Ⅱ,Ⅲ)are 2.04×10^(6),7.56×10^(6),1.48×10^(7) to Staphylococcus aureus,and 2.96×10^(6),1.01×10^(7),2.14×10^(7) to Escherichia coli after 12 h treatment.In addition,the interaction process between GA-CS copolymer and bacteria can be observed through a transmission electron microscope.The specific manifestation is that the bacterial cell membranes are ruptured after being treated with the copolymer,which causes the cell contents to flow out,and the cell morphology is shrunk and out ofshape.
基金Funded by the National Natural Science Foundation of China(Nos.81771080 and 8131147)the Opening Project of Hubei Key Laboratory of Purification and Application of Plant Anti-cancer Active Ingredients(No.HLPAI 2014006)the Health Commission of Hubei Province Scientific Research Project(No.WJ2019H275)
文摘A dual-receptor targeting delivery system based on acid-cleavage hydrazone bond was developed in the study. The characters of CMCS-hyd-CUR-EGFR-mAb were identified. The in vitro release studies revealed that this drug delivery system was acid-sensitive, and the self-assembled nanoparticles which were spherical. The in vitro results indicated that the dual-receptor targeting nanoparticles could be faster internalized into the Cal-27 cells via receptor-mediated endocytosis, which exhibited better antitumor activity than the one-receptor nanoparticles. The experimental results clearly reveal that CMCS-hyd-CUR-EGFR mAb provides a novel way for drug delivery in oral cancer treatment.
