关键词: 姜黄素, 纳米粒, 制备工艺, 工艺优化, 抗氧化, 工程化纳米材料

Abstract: BACKGROUND: Curcumin is the main active ingredient of turmeric and has significant medicinal value in anti-tumor, anti-inflammatory, antioxidant and other aspects. However, its poor water solubility, unstable chemical properties and easy decomposition lead to difficulty in extracting curcumin and low extraction yield. Therefore, it is particularly important to optimize the curcumin extraction method.
OBJECTIVE: To enhance the extraction yield and utilization value of curcumin and optimize the curcumin extraction process and curcumin nanoparticle preparation process. 
METHODS: Curcumin was extracted from turmeric by ethanol extraction, ultrasonic extraction, ionic liquid extraction, enzyme extraction, and ionic liquid combined with ultrasonic assisted enzyme extraction. The curcumin extraction yield was detected by high performance liquid chromatography; the best extraction method was determined, and subsequent process optimization experiments were carried out. The curcumin extraction yield was the response value with the type of ionic liquid, reaction temperature, ultrasonic time, liquid-to-solid ratio, ionic liquid concentration, and enzyme-drug mass ratio as parameters. The optimal production process of ionic liquid combined with ultrasonic assisted enzyme extraction was determined by single factor combined response surface experiment. The optimal process for preparing curcumin nanoparticles by ionic crosslinking method was determined by single factor combined response surface experiment with acetic acid concentration, chitosan to sodium tripolyphosphate mass ratio, stirring rate, curcumin mass concentration, sodium tripolyphosphate mass concentration, and chitosan mass concentration as parameters, and drug encapsulation efficiency as response value. Curcumin nanoparticles were prepared under the optimal process, and the particle size, polydispersity index, Zata potential value, drug loading, stability, hemolysis rate, and antioxidant capacity in vivo and in vitro of the nanoparticles were detected.
RESULTS AND CONCLUSION: (1) Among the five extraction methods, the curcumin yield of ionic liquid combined with ultrasound-assisted enzyme extraction was the highest, and this method was selected as the curcumin extraction method for subsequent experiments. The results of single factor combined response surface experiment showed that the optimal process for curcumin extraction was: ionic liquid selected 1-hexyl-3-methylimidazolium chloride, reaction temperature 55 ℃, liquid-to-solid ratio 40 mL/g, ultrasound time 57 minutes, ionic liquid concentration 57%, enzyme-drug mass ratio 3.5:10, and the obtained turmeric extraction yield was 3.10%. The optimal preparation process of curcumin nanoparticles was: glacial acetic acid concentration 0.5%, chitosan and sodium tripolyphosphate mass ratio 5.0:1, stirring speed 150 r/min, curcumin mass concentration 2.23 mg/mL, sodium tripolyphosphate mass concentration 1.45 mg/mL, chitosan mass concentration 3.63 mg/mL, and the obtained drug encapsulation efficiency was 90.61%. (2) The drug loading of curcumin nanoparticles was (14.49±0.23)%, the average particle size was (76.95±1.65) nm, the polydispersity coefficient was 0.15±0.02, and the Zata potential value was (32.37±1.46) mV. The curcumin nanoparticles had good stability and blood compatibility, did not induce hemolysis, and had stronger antioxidant capacity in vivo and in vitro than free curcumin. (3) The results show that the process optimization not only solves the problems of low extraction yield, poor solubility, and low bioavailability of curcumin, but also enhances its antioxidant activity in vivo and in vitro.

Key words: curcumin, nanoparticle, preparation process, process optimization, antioxidant, engineered nanomaterial