Reduction sensitive polyamino acid nano hydrogel and preparation method thereof

[0061] Add 1.1 g of aminated polyethylene glycol monomethyl ether with a number-average molecular weight of 550 to the dry reaction flask, remove water with 100 mL of anhydrous toluene at 130 ° C for 2 h, and vacuum dry the remaining Toluene; the obtained solid was dissolved in 10 mL of dry N,N-dimethylformamide to obtain the first solution; 2.06 g of γ-propynyl-L-glutamate-N-carboxylic acid anhydride was dissolved in 30 mL of dry In N,N-dimethylformamide, the second solution was obtained; in a nitrogen atmosphere, the first solution was mixed with the second solution, stirred under nitrogen protection conditions, and reacted at 40°C for 24h; after the reaction, reduce N,N-dimethylformamide was dried under pressure, and then the obtained solid was dissolved in chloroform, then settled with ether, filtered by suction, and dried to obtain polyethylene glycol monomethyl ether-poly(γ-propyne base-L-glutamate) block copolymer;

[0062] Dissolve 0.04 g of the obtained polyethylene ...

[0065] Add 1 g of aminated polyethylene glycol monomethyl ether with a number-average molecular weight of 2000 to the dry reaction flask, and remove the water by azeotroping with 100 mL of anhydrous toluene at 130°C for 2 h, then vacuum the remaining toluene to dryness ; The resulting solid was dissolved in 10 mL of dry N,N-dimethylformamide to obtain a first solution; 1.26 g of γ-propynyl-L-glutamate-N-carboxylic acid anhydride was dissolved in 20 mL of dry In N,N-dimethylformamide, the second solution was obtained; in a nitrogen atmosphere, the first solution was mixed with the second solution, stirred under nitrogen protection conditions, and reacted at 20°C for 72h; after the reaction, the pressure was reduced Drain N,N-dimethylformamide, then dissolve the obtained solid in chloroform, settle with ether, filter with suction, and dry to obtain polyethylene glycol monomethyl ether-poly(γ-propynyl -L-glutamate) block copolymer;

[0066] Dissolve 0.04 g of the obtained polyet...

[0069] Dissolve 0.04 g of the polyethylene glycol monomethyl ether-poly(γ-propynyl-L-glutamate) block copolymer obtained in Example 2 in 10 mL of N,N-dimethylformamide, and then Slowly add it dropwise into 20mL of ultrapure water, and after stirring for two hours, remove the organic solvent by dialysis to obtain a micellar solution of the polymer, add 0.01g of cross-linking agent to the micellar solution, and then blow it with nitrogen Soak for 30 minutes, add 0.003g CuSO 4 ·5H 2 0, after bubbling for 5 minutes, add 0.01g sodium ascorbate, seal, under nitrogen atmosphere, 25 ℃ of reaction 24h, after reaction finishes, reaction solution is added in the dialysis bag, with distilled water dialyzing for three days, freeze-drying then, That is, the polyamino acid nanohydrogel with a cross-linking degree of 50% is obtained.

[0070] The polyamino acid nano-hydrogel that embodiment 3 obtains is carried out in vitro simulated release experiment, and the result shows, the release of ...