Chitosan-based hepatic-targeted nano-particle drug delivery system and preparation method thereof
A drug delivery system and nanoparticle technology, which is applied in the field of chitosan-based liver-targeted nanoparticle drug delivery system and its preparation, can solve the problems of high efficiency, a large amount of materials and drug waste, operation parallelism, and low ball formation rate. Achieve good biocompatibility, reduce drug dosage and administration times, and improve drug efficacy
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Embodiment 1
[0020] Embodiment 1: Preparation of glycyrrhetinic acid-sulfate chitosan loaded doxorubicin nanoparticles
[0021] 1) Preparation of succinate glycyrrhetinic acid
[0022] Dissolve 10.0mmol of glycyrrhetinic acid and 40.0mmol of succinic anhydride in 100.0mL of pyridine, heat and reflux for 16 hours, concentrate the reaction solution under reduced pressure and then precipitate with water, adjust the pH to 3~4, filter, and recrystallize the solid with methanol aqueous solution , Vacuum drying, the resulting solid is succinate glycyrrhetinic acid.
[0023] 2) Preparation of glycyrrhetinic acid grafted sulfate chitosan
[0024] Dissolve 2.25g, 10.0mmol sulfate chitosan, molecular weight 50000, deacetylation degree 95%, sulfonation degree 0.8, in 112.5mL water and N,N-dimethylformamide mixed solution, water and N, The volume ratio of N-dimethylformamide is 1:10, the concentration of chitosan sulfate is 20.0mg / mL, add 20.0mmol succinate glycyrrhetinic acid, stir until the solutio...
Embodiment 2
[0029] Example 2: Preparation of Glycyrrhetinic Acid-Carboxymethyl Chitosan-loaded Paclitaxel Nanoparticles
[0030] 1) Preparation of glycyrrhetinic acid succinate: the same as in Example 1.
[0031] 2) Preparation of Glycyrrhetinic Acid Grafted Carboxymethyl Chitosan
[0032] 0.44g, 2.0mmol carboxymethyl chitosan, molecular weight 3000, deacetylation degree 90%, carboxylation degree 1.0, was dissolved in the mixed solution of 88.0mL water and N, N-dimethylformamide, water and N , the volume ratio of N-dimethylformamide is 1:1, the concentration of carboxymethyl chitosan is 5.0mg / mL, add 0.2mmol succinate glycyrrhetinic acid, stir until the solution is transparent, add 0.6mmol 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.6mmol N-hydroxysuccinimide were reacted at 25°C for 24 hours, acetone precipitated, the solid was dissolved in water, and the pH= 7-8, dialyze against water for 3 days, freeze-dry to obtain glycyrrhetinic acid-carboxymethyl chitosan, an...
Embodiment 3
[0035] Embodiment 3: Preparation of glycyrrhetinic acid-sulfate chitosan-loaded hydroxycamptothecin nanoparticles
[0036] 1) Preparation of glycyrrhetinic acid succinate: the same as in Example 1.
[0037] 2) Preparation of glycyrrhetinic acid grafted sulfate chitosan
[0038] 2.41g, 10.0mmol sulfate chitosan, molecular weight 200000, deacetylation degree 75%, sulfonation degree 1.0, was dissolved in 240.0mL water and N, N-dimethylformamide mixed solution, water and N, The volume ratio of N-dimethylformamide is 1:5, the concentration of chitosan sulfate is 10.0mg / mL, add 6.0mmol succinate glycyrrhetinic acid, stir until the solution is transparent, add 9.0mmol 1- (3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 9.0mmol N-hydroxysuccinimide, reacted at 55°C for 48 hours, precipitated with acetone, dissolved the solid in water, adjusted pH=7~ 8. Dialyze against water for 3 days, freeze-dry to obtain glycyrrhetinic acid-sulfate chitosan, and the substitution degre...
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