Abstract：OBJECTIVE To synthesize the polyethylene glycol(mPEG)-grafted chitosan coupled with deoxycholic acid, and to prepare the curcumin-loaded micelles and characterize their physicochemical properties. METHODS mPEG-chitosan-deoxycholic acid was synthesized by two steps, and its structure was characterized by IR, 1H NMR and the physical properties were charaterized by differential scanning calorimetry(DSC).The solubility of carrier was investigated in various solvents, and the solubilization capacity for insoluble drugs was also discussed.The preparation method of mPEG-CS-DA-Cur micelles was optimized, and the entrapment efficiency, drug loading, particle size distribution and drug release behavior were also characterized. RESULTS The drug-loaded nano-micelles prepared by dialysis method have the characteristics of high entrapment efficiency, small average particle size and no residual solvent,the drug loading of mPEG-CS-DA-Cur micelles was(12.11±1.52)%, the encapsulation efficiency was(89.37±4.12)%, and the average particle size was 161.4nm with uniform distribution .The drug release from the micelles was relativley slow and stable. CONCLUSION A new type of chitosan derivative with amphiphilic charateristics is synthesized in this study,and it will be an excellent micelle carriers. It shows high encapsulation efficiency and drug loading for curcumin,which provides a certain references for the follow-up drug targeting research.
陆肖枫, 戴盈英, 沈明丰, 刘扬, 胡晓波. 两亲性纳米胶束聚乙二醇接枝壳聚糖偶联脱氧胆酸-姜黄素的制备与评价[J]. 中国药学杂志, 2022, 57(19): 1660-1665.
LU Xiao-feng, DAI Ying-ying, SHEN Ming-feng, LIU Yang, HU Xiao-bo. Preparation and Evaluation of Amphiphilic Curcumin-Polyethylene Glycol-Grafted Chitosan Coupled with Deoxycholic Acid Micelles. Chinese Pharmaceutical Journal, 2022, 57(19): 1660-1665.
MARQUARDT J U, GOMEZ-QUIROZ L, THORGEIRSSON S S, et al. Curcumin effectively inhibits oncogenic NF-κB signaling and restrains stemness features in liver cancer[J]. J Hepatol, 2015, 63(3):661-669.
ZHANG W L,HE Z Y,ZHAO L, et al. Mechanism of curcumin reversing glucocorticoid resistance in chronic obstructive pulmonary disease[J]. Shandong Med J(山东医药), 2016, 56(38):1-4.
HASSANZADEH S, READ M I, BLAND A R, et al. Curcumin: an inflammasome silencer[J].Pharmacol Res, 2020, 159:104921. Doi: 10.1016/j.phrs.2020.104921.
YAO Q, KE Z, GUO S, et al. Curcumin protects against diabetic cardiomyopathy by promoting autophagy and alleviating apoptosis[J]. J Mol Cell Cardiol, 2018, 124:26-34. Doi: 10.1016/j.yjmcc.2018.10.004.
SONG L P,WANG Y. Research progress of curcumin pharmacological effect and mechanism[J]. China Med Her(中国医药导报), 2020, 17(20):29-34.
LIN X, BAI D, WEI Z, et al. Curcumin attenuates oxidative stress in RAW264.7 cells by increasing the activity of antioxidant enzymes and activating the Nrf2-Keap1 pathway[J]. PLoS One, 2019, 14(5):e0216711. Doi: 10.1371/journal.pone.0216711.
WANG T, CAI S Z, XU Q. Progress in preparation and application of PEGylated chitosans[J].Chemistry(化学通报), 2020, 83(6):536-545.
SONG P. Preparation of chitosan amphiphilic derivatives and the application as drug carriers[D]. Jinan:University of Jinan, 2012.
BEI Y Y. Study on the novel liver cancer targeting self-assembled micelles of harmine based on palmitoyl-trimethyl-chitosan[D]. Suzhou:Soochow University, 2013.
DAI P, ZHENG J L, LIU B R, et al. Chemical modification and application of chitin and chitosan[J]. Polym Bull(高分子通报), 2020, (7):1-17.
CHEN L F, SHEN X, LI R Y, et al. Synthesis and cytocompatibility of novel carboxymethyl chitosan-polylactic acid-polyethylene glycol copolymers[J]. Biomed Eng Clin Med(生物医学工程与临床), 2018, 22(5):506-510.
ZAINA A B. Study on PEGylated chitosan nanoparticle loaded with drug and its application[D].Shanghai:East China University of Science and Technology, 2019.
WANG H,YANG Z M,HE Z Y,et al. Preparation and physicochemical properties of amphiphilic chitosan/quercetin nanomicelles[J]. Chin J Trop Crop(热带作物学报), 2019, 40(5):980-986.
LI Y W,TIAN R,WANG X H,et al. Progress of polymeric micelle as vehicles for nanomedicine[J]. Polym Mater Sci Eng(高分子材料科学与工程), 2020, 36(1):167-174.
MA Z, WANG N, HE H, et al. Pharmaceutical strategies of improving oral systemic bioavailability of curcumin for clinical application[J]. J Controlled Release, 2019, 316: 359-380.
DOU J F,YIN M H,ZHOU Y B. Formulation Optimization and Characterization of Resveratrol Carboxymethyl Chitosan Microspheres[J].J Anhui Sci Technol Univ(安徽科技学院学报), 2017, 31(5):51-57.
LIU Y. Studies on lung tumor-targeting drug delivery system oflow density lipoprotein mediated self-assembled micelles[D]. Suzhou:Soochow University, 2014.
WANG H, YANG Z, HE Z, et al. Self-assembled amphiphilic chitosan nanomicelles to enhance the solubility of quercetin for efficient delivery[J]. Colloids Surf B Biointerfaces, 2019, 179:519-526. Doi: 10.1016/j.colsurfb.2019.04.007.