N-(4-咪唑甲基)-羟乙基壳聚糖自组装胶束载槲皮素的研究  

Research on self-assembly micelles of N-(4-methylimidazole)-hydroxyethyl-chitosan loading quercetin

作　　者：夏晓静[1,2] 胡英[2] 金江[2] 徐蓓华[2] 周建平[1] 

机构地区：[1]中国药科大学药剂学教研室,南京210009 [2]浙江医药高等专科学校,宁波315100

出　　处：《中国药科大学学报》2017年第1期46-52,共7页Journal of China Pharmaceutical University

基　　金：宁波市自然科学基金资助项目(No.2014A610203;No.2014A610212);浙江省教育厅课题资助项目(No.Y201226180);宁波市科技创新团队资助项目(No.2015C110027)~~

摘　　要：为了提高天然黄酮类化合物槲皮素的水溶性,将天然高分子材料壳聚糖进行两亲性衍生化制成N-(4-咪唑甲基)-羟乙基壳聚糖(MHC),作为槲皮素自组装聚合物胶束载体,并采用~1H NMR、元素分析法、芘荧光光谱法等进行了表征;同时采用单因素考察法进行了MHC-槲皮素胶束的工艺优化。结果表明,载体浓度为0.67%、槲皮素与MHC质量比为1∶10时可以获得粒径为(99.21±1.71)nm,Zeta电位为+(20.01±0.72)m V,载药量为(5.42±0.32)%的聚合物胶束;其体外释药曲线符合Higuchi方程Q=0.110 1t^(1/2)-0.064。槲皮素胶束和槲皮素溶液剂静脉注射给药后,在大鼠体内平均滞留时间分别是21.42和0.30 h,AUC_(0-t)分别为57.49和2.50μg·h/m L,表明采用MHC为载体材料的槲皮素自组装胶束具有较好的增溶、缓释以及提高生物利用度的作用,可作为槲皮素等抗肿瘤药物的载体。To improve the solubility of quercetin（ QT）,one of flavonoids that can inhibit the proliferation of various types of cancer cells,the novel amphiphilic polymer N-（ 4-methylimidazole）-hydroxyethyl-chitosan（ MHC）,synthetized by chemical derivatization from chitosan,was used as the self-assembly micelles of QT.The formed polymer was characterized by ^1 H NMR,elemental analysis and pyrene fluorescence spectrometry.The formulation of MHC micelles loading quercetin was optimized through single factor experiment.Then the optimized formulation was obtained as follows： the concentration of MHC was 0.67% and the ratio of drug and carrier was 1 ∶ 10.The micelles particle size was（ 99.21 ± 1.71） nm,Zeta potential was ＋（ 20.01 ± 0.72） m V and drug loading was（ 5.42 ± 0.32） %.The in vitro release curve was investigated and was found to conform to Higuchi equation of Q = 0.1101 t^1/2- 0.064.The results of in vivo experiment showed that the mean rentention time and bioavailability of the MHC-QT micelles were 21.42 h and 57.49 μg · h/m L,respectively,compared to 0.30 h and2.50 μg · h/mL of the free QT solution.These indicated that the MHC micelles could significantly improve the solubility of QT,the drug sustained-release effect and bioavailability,which would used as carrier for the antitumor drugs.

关 键 词：槲皮素 N-(4-咪唑甲基)-羟乙基壳聚糖 自组装胶束 药代动力学 

分 类 号：R943[医药卫生—药剂学]